Klinische Studien

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Sebastian Bauer

sebastian.bauer@uk-essen.de

Hufelandstr. 55
45147 Essen

Indikation
Sarkome

Medizinischer Befund
Metastatic and\/or Unresectable Soft Tissue Sarcoma 

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Halime Kalkavan

halime.kalkavan@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
Subprotocol A, B, and C

-- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
-- Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before AMG 193 dosing.
-- Homozygous MTAP-deletion.
-- Able to swallow and retain PO administered study treatment.
-- Disease measurable as defined by RECIST v1.1.

Subprotocol A
- Histologically or cytologically confirmed diagnosis of NSCLC.
Arm A (AMG 193 + carboplatin + paclitaxel + pembrolizumab):
- Predominantly squamous histology.
Arm B (AMG 193 + carboplatin + pemetrexed + pembrolizumab):
- Predominantly non-squamous histology.
Arm C (AMG 193 + pembrolizumab):
- PD-L1 positive.

Subprotocol B
- Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.

Subprotocol C
-- Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases.
-- Brain lesion meeting RANO-BM criteria for measurable disease.

Ausschlusskriterien
Subprotocol A, B, and C

- Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
- Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
- History of solid organ transplant.
- Major surgery within 28 days of first dose of AMG 193.
- Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
- Radiation therapy within 28 days of first dose.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Thoracic Tumors\nNon-small Cell Lung Cancer (NSCLC)

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Isabel Virchow

Hufelandstr 55
45147 Essen

Sponsor

AMGEN GmbH

+49 89 149096 0

Riesstraße 24
80992 München

Einschlusskriterien
pathologically documented metastatic colorectal adenocarcinoma
central confirmation of KRAS p.G12C mutation
measurable disease per RECIST v1.1 criteria. Lesions previously radiated are
not considered measurable unless they have progressed after radiation
age 18 years (or legal age within the country if it is more than 18 years)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 1
life expectancy of 6 months, in the opinion of the investigator
adequate hematologic and end organ function
ability to take oral medications and willing to record daily adherence to
investigational product

Ausschlusskriterien
prior systemic therapy for metastatic disease except for a maximum of 1 dose of
SOC FOLFIRI (chemotherapy backbone) administered during the screening
period
active, untreated brain metastases
leptomeningeal disease
tumor is known to have B-raf proto-oncogene serine/threonine kinase
(BRAF) V600E mutation
tumor is known to be microsatellite instability high (MSI-H)
previous treatment with a KRAS p.G12C inhibitor
known dihydropyrimidine dehydrogenase (DPD) deficiency
known UDP-glucuronosyltransferase 1A1 (UGT1A1)*28 homozygosity or
diagnosis of
subject has required a dose reduction or dose delay of either 5-fluorouracil
(5-FU) or irinotecan in any prior chemotherapy regimen in the past for toxicity, to
history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial
pneumonitis or pulmonary fibrosis on baseline CT scan

Studienteilnehmende Mindestalter
18 Jahr(e)

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
Treatment-naïve Subjects With Metastatic Colorectal Cancer With KRAS p.G12C Mutation

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Isabel Virchow

Hufelandstr 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
1. Age = 18 years (or > legal age within the country if it is older than 18 years).
2. Pathologically documented, locally-advanced or metastatic malignancy with any missense mutation in the KRAS gene or evidence of KRAS amplification using an analytically validated KRASWT amplification assay.
3. Participants must have no standard of care treatment options or have actively refused such therapy.
4. Able to swallow and retain per oral administered study treatment.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as determined by the site investigator.
7. Adequate organ function.
8. Archival (formalin-fixed, paraffin-embedded [FFPE]) tumor tissue or block collected within 5 years before screening must be available. Participants without archived tumor tissue may undergo tumor biopsy before AMG 410 dosing (Day1).

Ausschlusskriterien
1. Untreated symptomatic central nervous system or leptomeningeal metastases.
2. Uncontrolled pleural effusion and/or ascites.
3. History of other malignancy within the past 5 years.
4. Active systemic infection or symptoms that indicate an acute and/or uncontrolled infection requiring IV antibiotics within 7days prior to the first dose of study treatment.
5. History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis).
6. Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of study treatment.
7. History of solid organ transplant.
8. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of study treatment.
9. Presence or history of any of the following viral infections: HIV, Hepatitis C, Hepatitis B, and active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
10. Toxicities from prior anti-tumor therapy (including radiotherapy) not having improved to at least Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1.
11. Therapeutic or palliative radiation therapy within 2 weeks of first dose of study treatment.
12. Major surgery within 28 days of first dose of study treatment.
13. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Solide Tumoren

Medizinischer Befund
KRAS Altered Advanced or Metastatic Solid Tumors

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Martin Schuler

martin.schuler@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
Participants are eligible to be included in the study only if all of the following criteria apply:
• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
• Histologically or cytologically confirmed small-cell lung cancer (SCLC).
• Diagnosed and treated for LS-SCLC with concurrent chemotherapy and radiotherapy.
• Has completed chemoradiotherapy without progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1.) (ie, achieved complete response [CR], partial response [PR], or stable disease [SD]).
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
• Minimum life expectancy of 12 weeks.
• Adequate organ function.
• Toxicities attributed to concurrent chemoradiotherapy resolved to grade ≤ 1, unless otherwise specified. Excluding alopecia or fatigue.

Ausschlusskriterien
Participants are excluded from the study if any of the following criteria apply:
Disease Related
• Extensive-stage SCLC (ES-SCLC).
• Any previous diagnosis of transformed non-small-cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that has transformed to SCLC, or mixed SCLC NSCLC histology.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis. Other Medical Conditions
• History of other malignancy within the past 2 years, with certain exceptions.
• History of solid organ transplantation.
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment.
• History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
• Exclusion of human immunodeficiency virus (HIV) and hepatitis infection based on criteria per protocol.
• Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study treatment.

Prior/Concomitant Therapy
• Received sequential chemotherapy and thoracic radiotherapy (no overlap of thoracic radiotherapy with chemotherapy) during chemoradiation.
• Prior therapy with any selective inhibitor of the delta-like ligand 3 (DLL3) pathway.
• Prior history of severe or life-threatening events from any immune-mediated therapy.
• Receiving another anti-cancer therapy. Adjuvant hormonal therapy for resected breast cancer is permitted.
• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
• Major surgical procedures within 28 days prior to first dose of study treatment.
• Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines and live viral non-replicating vaccines within 3 days prior to first dose of study treatment.
• Prior/Concurrent Clinical Study Experience
• Treatment in an alternative investigational trial within 28 days prior to enrollment.

Other Exclusions
• Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 72 days after the last dose of study treatment.
• Female participants who are breastfeeding or who plan to breastfeed while on study through 72 days after the last dose of study treatment.
• Female participants planning to become pregnant or donate eggs while on study through 72 days after the last dose of study treatment.
• Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.
• Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 132 days after the last dose of study treatment.
• Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 132 days after the last dose of study treatment.
• Male participants unwilling to abstain from donating sperm during treatment and for an additional 132 days after the last dose of study treatment.
• Participant has known sensitivity to any of the products or components to be administered during dosing.
• Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.
History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Limited-Stage Small-Cell Lung Cancer (LS-SCLC)\nSmall Cell Lung Cancer (SCLC)

MedDRA Term
Small cell lung cancer limited stage

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Michael Pogorzelski

michael.pogorzelski@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
• Participants = 18 years of age (or legal adult age within country) at time of signing informed consent.
• Participants with histologically or cytologically confirmed ES-SCLC.
• For Parts 1 and 2, participant must have ES-SCLC that has progressed or recurred following at least 1 line of platinum-based anti-cancer therapy.
• For Part 3, participants must have ES-SCLC and no prior systemic treatment for ES SCLC other than 1 cycle of platinum-based chemotherapy, etoposide, and PD-(L)1 inhibitor in the first-line setting.
• At least 1 measurable lesion as defined by RECIST 1.1.
• Participants must have adequate organ function (cardiac, pulmonary, kidney, bone marrow, and liver).

Ausschlusskriterien
• Prior delta-like ligand 3 (DLL3) or B7 homolog 3 (B7-H3) targeted therapy.
• Prior exposure to topoisomerase I inhibitors or antibody-drug conjugate (ADC) with topoisomerase I inhibitor payload.
• Symptomatic central nervous system (CNS) metastases. Note: Participants with asymptomatic brain metastases are eligible as defined in the protocol.
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Baseline requirement of supplemental oxygen.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
99 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs, Phase I Studie

Medizinischer Befund
Small Cell Lung Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Viktor Grünwald

+49 (0)201 723-3213
urologie.studien@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
- Parts 1, 2, and 5: prior taxane exposure Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone acetate and/or enzalutamide, apalutamide, darolutamide, bicalutamide, or equivalent) and have failed at least 1 (but not more than 2) taxane regimens including for mHSPC (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Note: A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane.
1. Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.
2. Dose expansion phase: participants must not have had more than 2 NHTs and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-PD1, PARP inhibitors, radioligand therapies, sipuleucel-T, experimental agents) Note: Combinations are considered one systemic anti-cancer treatment.
- Parts 4A and 4B: prior taxane exposure
1. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) given for hormone-sensitive prostate cancer (HSPC) or non-metastatic CRPC and have failed up to 1 taxane regimen which must have been given for HSPC only (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen).
2. 4A: Participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible).
3. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
- Parts 3 and 4C: no prior taxane exposure
a. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen.
- Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist.
- Total serum testosterone <= 50 ng/dL or 1.7 nmol/L.
- Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria:
1. PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
2. nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications.
3. appearance of 2 or more new lesions in bone scan.
- Eastern Cooperative Oncology Group performance status of 0-1.
- Adequate organ function, defined as follows:
1. Hematological function:
a. absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment).
b. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment).
c. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).
2. Renal function:
1. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation >= 30 ml/min/1.73 m^2.
3. Hepatic function:
a. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement).
b. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases).
4. Cardiac function:
a. left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available).
b. Baseline electrocardiogram (ECG) QTcF <= 470 msec.

Ausschlusskriterien
- Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma.
- Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose).
- Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
- Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
- History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of AMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation.
- Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509 with the exception of ischemia or non-ST segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of AMG 509.
- Any anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist/antagonist). Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich

Indikation
Urogenitale Tumore

Medizinischer Befund
Metastatic Castration-Resistant Prostate Cancer (mCRPC)

MedDRA Term
Castration-resistant prostate cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Stefan Kasper-Virchow

+49 (0) 201 723-2040
stefan.kasper-virchow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
* Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
* Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas.
* Tumor tissue (FFPE sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before dosing.
* Homozygous MTAP-deletion.
* Disease measurable as defined by RECIST v1.1.
* Adequate organ function as defined in the protocol

Ausschlusskriterien
* Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
* Radiation therapy within 28 days of first dose.
* Major surgery within 28 days of first dose of AMG 193.
* Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
* Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
* History of solid organ transplantation.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
100 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
Locally advanced or met. PDAC with MTAP deletion (Gastrointestinal, Biliary Tract, and Pancreatic Cancers)

MedDRA Term
Biliary cancer metastatic, Ductal adenocarcinoma of pancreas

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Michael Pogorzelski

michael.pogorzelski@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Amgen Inc, USA

Einschlusskriterien
101 Participant has provided informed consent before initiation of any study-specific
activities/procedures.
102 Age = 18 years or = legal age within the country if it is older than 18 years.
103 Histologically or cytologically documented extensive-stage small-cell lung cancer
(American Joint Committee on Cancer, 2017, Stage IV SCLC [T any, N any, M1
a/b/c]), or T3 to T4 due to multiple lung nodules that are too extensive or have
tumor/nodal volume that is too large to be encompassed in a tolerable radiation
plan.
104 Measurable disease as defined per RECIST 1.1
105 No prior treatment for SCLC.
? Individuals whose disease has progressed after prior curative intent treatment for
limited stage small-cell lung cancer (LS-SCLC) [i.e. chemoradiation therapy +/-
anti PD-(L)1 consolidation, where approved] are eligible if 6 months or more have
elapsed from end of all treatments and progression date, after consultation with
medical monitor.
106 Suitable to receive carboplatin, etoposide and durvalumab regimen as first-line
treatment per investigator clinical assessment.
107 Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
108 Minimum life expectancy = 12 weeks.
109 Adequate organ function, defined as follows:
? Hematological function:
o absolute neutrophil count = 1.5 x 10^9/L
o platelet count = 100 x 10^9/L
o hemoglobin = 9 g/dL (90 g/L)
? Coagulation function:
o prothrombin time (PT)/international normalized ratio (INR) and partial
thromboplastin time (PTT) or activated partial thromboplastin time
(APTT) = 1.5 x institutional upper limit of normal (ULN) except for
participants receiving anticoagulation, who must be on a stable dose
of anticoagulant therapy for 2 weeks prior to randomization
? Renal function:
o estimated glomerular filtration rate (eGFR) based on Modification of
Diet in Renal Disease (MDRD) calculation = 60 mL/min/1.73 m2
? Hepatic function:
o aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) = 3 x ULN (or = 5 x ULN for participants with liver involvement)
o total bilirubin (TBL) = 1.5 x ULN (or = 2 x ULN for participants with
liver involvement), with the exception of participants with Gilbert's
disease
? Pulmonary function:
o No oxygen supplementation
? Cardiac function:
o Cardiac ejection fraction = 50%, no clinically significant pericardial
effusion as determined by an echocardiogram (ECHO) [or multigated
acquisition (MUGA) scan if ECHO is not available], and no
electrocardiogram (ECG) finding related to acute/subacute
myocardial ischemia and/or clinically significant arrythmia.

Ausschlusskriterien
5.2 Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Disease Related
201 Symptomatic central nervous system (CNS) metastases, or leptomeningeal
disease.
? Participants with untreated brain metastases that are asymptomatic and do not
require corticosteroids, nor local therapy per investigators standard of practice
are eligible.
? Participants with treated brain metastases are eligible provided the following
criteria are met:
- Radiation treatment was completed at least 2 weeks prior to first dose of
study treatment (stereotactic radiosurgery completed at least 7 days prior to
first dose of study treatment)
- Participant is clinically stable and on stable or decreasing doses of steroids
(total daily dose ? 10 mg prednisone or equivalent) prior to first dose of study
treatment
Product: AMG 757 Tarlatamab
Protocol Number: 20240178
Date: 07 February 2025 Page 51 of 217
CONFIDENTIAL
- Participant is off or on stable doses of anti-epileptic drugs at least 14 days
prior to first dose of study treatment
202 Any previous diagnosis of transformed non-small-cell lung cancer (NSCLC),
epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that
has transformed to SCLC, or mixed SCLC NSCLC histology.
? Participants with mixed histology tumors with predominant SCLC histology
are allowed.
Other Medical Conditions
203 History of other malignancy within the past 2 years, with the following exceptions:
- Malignancy treated with curative intent before enrollment, with no known active
disease and felt to be at low risk for recurrence by the treating physician, after
discussion with the medical monitor.
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Adequately treated breast ductal carcinoma in situ without evidence of disease.
- Prostatic intraepithelial neoplasia without evidence of prostate cancer.
- Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ.
204 Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn’s disease], systemic lupus
erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves’ disease,
rheumatoid arthritis, hypophysitis, uveitis, etc.), autoimmune pneumonitis, and
autoimmune myocarditis. The following are exceptions to this criterion:
- Participants with vitiligo or alopecia.
- Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement.
- Any chronic skin condition that does not require systemic therapy.
- Participants without active disease in the last 5 years may be included but only
after consultation with the medical monitor.
- Participants with coeliac disease controlled by diet alone.
205 Myocardial infarction and/or symptomatic congestive heart failure (New York
Heart Association > class II) within 6 months prior to first dose of study treatment.
206 History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6
months prior to first dose of study treatment.
207 Evidence of interstitial lung disease (ILD) or active, non-infectious pneumonitis.
208 History of solid organ transplant.
209 Major surgical procedures within 28 days prior to first dose of study treatment.
210 Presence of active HIV or active hepatitis infection.
211 History of allergic reactions or acute hypersensitivity reactions to antibody
therapies, carboplatin, etoposide or pegfilgrastim.
212 Participant with symptoms and/or signs of systemic infection requiring parental or
oral antibiotics within 7 days prior to the first dose of study treatment.
Prior/Concomitant Therapy
213 Prior history of severe or life-threatening events from any immune-mediated
therapy.
214 Receiving systemic corticosteroid therapy or any other form of
immunosuppressive therapy within 14 days prior to first dose of study treatment:
- Low-dose corticosteroids (prednisone ? 10 mg per day or equivalent is permitted
during the study).
215 Treatment with live virus, including live-attenuated vaccination, within 4 weeks
prior to the first dose of study treatment. Inactive vaccines (eg, non-live or nonreplicating
agent) and live viral non-replicating vaccines (eg, Jynneos for mpox
infection) within 30 days prior to first dose of study treatment.
216 Receiving another anticancer therapy. Adjuvant hormonal therapy for resected
breast cancer is permitted.
217 Has received or is planning to receive consolidative chest radiation, for
extensive-stage disease.
Prior/Concurrent Clinical Study Experience
218 Participation in a tarlatamab clinical trial or prior therapy with any selective
inhibitor of the DLL3 pathway.
219 Treatment in an alternative investigational trial within 28 days prior to enrollment.
Other Exclusions
220 Participants of childbearing potential unwilling to use protocol-specified method
of contraception during treatment and for an additional:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
221 Participants who are breastfeeding or who plan to breastfeed while on study
through:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
222 Participants planning to become pregnant while on study through:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
223 Participants of childbearing potential with a positive pregnancy test assessed at
screening by a highly sensitive urine or serum pregnancy test.
Product: AMG 757 Tarlatamab
Protocol Number: 20240178
Date: 07 February 2025 Page 53 of 217
CONFIDENTIAL
224 Participants with a partner of childbearing potential who are unwilling to practice
sexual abstinence (refrain from heterosexual intercourse) or use contraception
during treatment and for an additional:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
225 Participants with a pregnant partner who are unwilling to practice abstinence or
use a condom during treatment and for an additional:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
226 Participants unwilling to abstain from donating sperm during treatment and for an
additional:
? 60 days following the last dose of tarlatamab.
? 6 months following the last dose of carboplatin and/or etoposide.
? 90 days following the last dose of durvalumab.
227 Participant has known sensitivity to any of the products or components to be
administered during dosing.
228 Participant likely to not be available to complete all protocol-required study visits
or procedures, and/or to comply with all required study procedures (eg, Clinical
Outcome Assessments) to the best of the Participant and investigator’s
knowledge.
229 History or evidence of any other clinically significant disorder, condition, or
disease (except for those outlined above) that, in the opinion of the investigator
or Amgen physician, if consulted, would pose a risk to participant safety, or
interfere with the study evaluation, procedures or completion.

Indikation
Lungenkrebs

Medizinischer Befund
Untreated Extensive Stage Small-Cell Lung Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Charité - Universitätsmedizin Berlin

Einschlusskriterien
* Patient has provided written informed consent
* Patient* 18 years or older at time of signing the informed consent form
* Histologically or cytologically confirmed metastatic stage IV non-squamous NSCLC
* Negative local testing for TTF-1
* Negative molecular testing for EGFR mutations and ALK rearrangements (tested locally). Exception: In specific individual cases, treatment can be initiated prior to receiving molecular diagnostics after consulting with the sponsor, if the local principal investigator assesses the likelihood of an EGFR mutation or ALK fusion to be negligible. However, this should only be done in exceptional cases if the patient has particularly high demand for treatment. If it is subsequently found that patients are positive for EGFR mutations and/or ALK rearrangements, they must be withdrawn from the study immediately and must not receive any further study medication. Instead, patients should receive adequate SOC therapy outside the study.
Awaiting results for molecular testing remains standard procedure for patient inclusion.
* PD-L1 tumor proportion score (TPS) < 50%, tested locally by QUiP®-certified immunohistochemistry
* ECOG performance status = 1
* Measurable lesions according to RECIST v1.1
* Life expectancy = 12 weeks
* Adequate hepatic, renal and bone marrow function
- Hemoglobin = 8.0 g/dL
- Absolute neutrophil count = 1.5 x 109/L
- Platelets = 100 x 109/L
- Calculated creatine clearance = 50 mL/min as determined by the Cockcroft-Gault equation and/or creatinin = 1,5x upper limit of normal (ULN)
- Serum bilirubin = 1.5 x institutional ULN
- AST/ ALT and alkaline phosphatase = 2.5 x ULN
- International normalized ratio (INR)/ Activated partial thromboplastin time (aPTT) =1.5 × ULN unless participant is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants
* The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
* Female patients who are considered as woman of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as up to 6 months after the last dose of study treatment. Male patients who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as at least 6 months after the last dose of IMP. Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic male patients do not require contraception

Ausschlusskriterien
* Mixed histologies (small-cell and non-small cell or non-squamous and squamous; patients exhibiting the latter expression pattern may be eligible if the non-squamous part predominates)
* Patients having received:
- Systemic treatment for metastatic or locally advanced disease
- prior PD-1/PD-L1 immunotherapies (prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte associated protein 4 [anti-CTLA-4], anti T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains [anti-TIGIT], anti-PD-1 and anti-PD-L1 therapeutic antibodies)
* Symptomatic, neurologically unstable CNS metastases or requiring increasing doses of steroids to manage CNS symptoms within 2 weeks prior to study entry (maximal acceptable dose must be ? 10 mg of prednisolone). Patients with asymptomatic, incidentally detected CNS metastases may be enrolled. Palliative radiotherapy for asymptomatic brain metastases (and any other, non-brain metastases, e.g. bone metastases) may be conducted after study entry.
* Leptomeningeal disease
* History of interstitial lung disease
* Severe infection within 2 weeks prior to study entry. Clinical signs must have been resolved to CTCAE grade ? 1
* Active infection with hepatitis B or C virus (HBV, HCV), human immunodeficiency virus (HIV) or Mycobacterium tuberculosis
* Known additional malignancies other than NSCLC, either untreated or having required active treatment within the past 3 years
* Significant cardiovascular disease (? NYHA 3)
* Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener's syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
- Patients with controlled Type I diabetes mellitus on an insulin regimen
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
* Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab/pembrolizumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Live vaccine within 30 days prior to first dose of trial treatment
* Known allergy or hypersensitivity to any component of the chemotherapy regimen or to atezolizumab or pembrolizumab or any constituents of the products
* Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.
* Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Non-Small Cell Lung Cancer Metastatic

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Isabel Virchow

Hufelandstr 55
45147 Essen

Sponsor

Astra Zeneca AB, Schweden

Einschlusskriterien
• HER2 positive for gastric cancer on a tumor biopsy.
• PD-L1 combined positive score (CPS) = 1.
• Provision of tumor tissue sample from recent biopsy adequate for HER2 and PD-L1 testing.
• Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma.
• WHO or Eastern Cooperative Oncology Group performance status of 0 or 1.
• Have measurable target disease assessed by the Investigator based on RECIST v1.1.
• Have adequate organ and bone marrow function within 14 days before randomization.
• LVEF = 55% within 28 days before randomization.
• Adequate treatment washout period before randomization.

Ausschlusskriterien
• Lack of physiological integrity of the upper gastrointestinal tract.
• Known dihydropyrimidine dehydrogenase enzyme deficiency.
• Contraindication to pembrolizumab or trastuzumab, contraindications to fluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.
• Persistent toxicities caused by previous anti-cancer therapy.
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring corticosteroid or anticonvulsant may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
• Uncontrolled infection including tuberculosis and active hepatitis A infection.
• Uncontrolled infection requiring intravenous (IV) antibiotics, anti-virals, or antifungals.
• Recent receipt of live, attenuated vaccine.
• Chronic/active HBV or HCV infection unless controlled.
• Clinically significant cardiac or psychological conditions.
• Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
• History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Lung-specific intercurrent clinically significant illnesses.
• Any active non-infectious skin disease requiring systemic treatment.
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART).
• History of any of the following: drug-induced severe cutaneous adverse reaction.
• Any concurrent antic-ancer treatment with the exception of receptor activator of nuclear factor kappa-B ligand inhibitors.
• Have had major surgical procedure recently (excluding placement of vascular access) or recent significant traumatic injury or an anticipated need for major surgery during the study.
• Current or prior use of immunosuppressive medication within 14 days before study intervention.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
HER2-positive Gastric Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Bristol-Myers Squibb

Einschlusskriterien
Non-squamous (NSQ), Stage IV or Recurrent Non-small Cell Lung Cancer and with Tumor Cell PD-L 1 expression of 1 % to 49%

Ausschlusskriterien
• Participants must not be pregnant and/or breastfeeding.
• Participants with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS-1 mutations that are sensitive to available targeted inhibitor therapy. Participants with unknown EGFR, ALK, or ROS-1 status are excluded.
• Participants with known BRAFV600E mutations, that are sensitive to available targeted inhibitor therapy; participants with known activating rearranged during transfection (RET) mutations or neurotrophic tyrosine receptor kinase (NTRK) fusion gene alterations are excluded. Participants with unknown or indeterminate BRAF mutation, activating RET mutations or NTRK fusion gene alterations are eligible.
• Participants must not have untreated central nervous system (CNS) metastases.
• Participants must not have leptomeningeal metastases (carcinomatous meningitis).
• Participants must not have concurrent malignancy requiring treatment.
• Participants must not have an active autoimmune disease.
• Participants must not have history of interstitial lung disease or pneumonitis that required oral or intravenous (IV) glucocorticoids to assist with management.
• Participants must not have a history of myocarditis.
• Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or other antibody or drug targeting T-cell co-stimulation or checkpoint pathways.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Lung cancer, non-squamous (NSQ), stage IV \nrecurrent non-small cell lung cancer and with tumor cell PD-L 1 expression of 1 % to 49%

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Stefan Kasper-Virchow

+49 (0) 201 723-2040
stefan.kasper-virchow@uk-essen.de

Hufelandstraße 55
45147 Essen

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
Colorectal Cancer

Institute
Innere Klinik (Tumorforschung), Klinik für Kinderheilkunde III, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. Uta Dirksen

+49 (0)201 723-82025
uta.dirksen@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinik Essen (AöR)

+49 (0)201 723-0
info@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
Diagnosis: Histologically confirmed, localized or metastatic EwS or Ewing-like sarcoma of bone and/or soft tissue
lnformed consent form (ICF): According to national and GCP guidelines and signed prior to registry entry

Ausschlusskriterien
Withdrawal from ICF

Geschlecht
Divers, Männlich, Weiblich

Indikation
KIK-Onko, Sarkome

Medizinischer Befund
Ewing Sarcomas (EwS) and related small round cell sarcomas (SRCSs)

Institute
Klinik für Nuklearmedizin, Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Ken Herrmann

+49 (0) 201 723 2032
ken.herrmann@uk-essen.de

Hufelandstr 55
45147 Essen

Sponsor

Novartis Pharma Schweiz AG

+41 41 763 71 11

Suurstoffi 14
6343 Rotkreuz

Einschlusskriterien
• Age = 18 years old
• Patients with one of the following indications:
• Locally advanced unresectable or metastatic PDAC who have received prior treatment with at least 1 line of cytotoxic chemotherapy, unless patient was ineligible to receive such therapy
• Locally advanced unresectable or metastatic NSCLC without any actionable genomic alterations who have received prior treatment with chemotherapy and immunotherapy, unless patient was ineligible to receive such therapy, or locally advanced unresectable or metastatic NSCLC with an actionable genomic alteration who have received prior treatment with targeted therapy, unless patient was ineligible to receive such therapy
• Locally advanced unresectable or metastatic HR+/HER2- ductal or lobular BC with disease progression following, or intolerance to, at least 2 lines of therapy
• Locally advanced unresectable or metastatic TNBC with disease progression following, or intolerance to, at least 2 lines of therapy
• (Dose escalation part only) Locally advanced or metastatic unresectable CRC who have received prior therapy with at least 1 line of cytotoxic chemotherapy, unless patient was ineligible to receive such therapy. Patients with known microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status must also have received immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
• Patients must have lesions showing 68Ga-NNS309 uptake

Ausschlusskriterien
• Absolute neutrophil count (ANC) < 1.5 x 109/L, hemoglobin < 10 g/dL, or platelet count < 100 x 109/L
• QT interval corrected by Fridericia's formula (QTcF) = 470 msec
• Creatinine clearance < 60 mL/min
• Unmanageable urinary tract obstruction or urinary incontinence
• Radiation therapy within 4 weeks prior to the first dose of [177Lu]Lu-NNS309

Other protocol-defined inclusion/exclusion criteria may apply.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs, Brustkrebs, Tumoren der Leber und Bauchspeicheldrüse und der Gallenwege, Tumoren des Magen-Darm-Traktes

Medizinischer Befund
Pancreatic Ductal Adenocarcinoma\nNon-small Cell Lung Cancer\nHR+\/HER2- Ductal and Lobular Breast Cancer\nTriple Negative Breast Cancer\nColorectal Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Martin Metzenmacher

martin.metzenmacher@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

AIO-Studien-gGmbH, Berlin

Einschlusskriterien
Patients who meet all of the following criteria are eligible for the project:

Age ≥ 18 years
Able to understand and willing to sign written Informed Consent and to complete patient-reported-outcome assessment instruments
Main project (Metatstatic NSCLC):

Confirmed non-small cell lung cancer (NSCLC)
Informed consent no later than four weeks after start of first-line systemic treatment
Stage IV, or stage IIIB/C (UICC8) if patient is ineligible for curative surgery and/or radiochemotherapy
Systemic therapy
Satellite Stage II/III (NSCLC):

Confirmed non-small cell lung cancer (NSCLC)
Informed consent no later than four weeks after start of first anti-tumor treatment
Stage II, stage IIIA, or stage IIIB/C (UICC8) if patient is eligible for curative surgery and/or radiochemotherapy
Systemic (chemo)therapy and/or radiation therapy and/or surgery
Satellite SCLC

Confirmed Small cell lung cancer (SCLC)
Informed consent no later than four weeks after start of first anti-tumor treatment or no later than four weeks after diagnosis for patients receiving "best supportive care only" (i.e. no anti-tumor treatment = no surgery, radiotherapy or systemic therapy)
Systemic (chemo)therapy and/or radiation therapy and/or surgery or best supportive care

Ausschlusskriterien
none

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Metastatic Non-small Cell Lung Cancer (NSCLC)\nNon-small Cell Lung Cancer Metastatic\nNon-small Cell Lung Cancer Stage I\nNon-small Cell Lung Cancer Stage II\nNon Small Cell Lung Cancer Stage III\nSmall-cell Lung Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Daiichi Sankyo Inc., USA

Einschlusskriterien
- Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
- Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
- Has histologically or cytologically documented SCLC.
- The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
- Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy-free interval of >30 days.
- Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
- Has documentation of radiological disease progression on or after the most recent systemic therapy.
- Has ECOG PS of ≤1.
- Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases that are no longer symptomatic (ie, without neurologic signs or symptoms) and who require no treatment with steroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Subjects must have a stable neurologic status for at least 2 weeks prior to the first dose of study drug.

Ausschlusskriterien
- Has received prior treatment with orlotamab, enoblituzumab, or other humanized anti-B7 homologue 3 (B7-H3) targeted agents, including I-DXd.
- Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
- Has received any of the comparators used in this study or any topoisomerase I inhibitor.
- Has inadequate washout period before randomization as specified in the protocol.
- Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
- Has uncontrolled or significant cardiovascular disease.
- Has clinically significant corneal disease.
- Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
- Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Non small-cell lung cancer (NSCLC)

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Martin Metzenmacher

martin.metzenmacher@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Astra Zeneca AB, Schweden

Einschlusskriterien
• Participant must be = 18 years at the time of screening
• Histologically proven diagnosis of pleural mesothelioma with known histology (epithelioid vs. non-epithelioid)
• Advanced unresectable disease that cannot be treated with curative surgery (with or without chemotherapy)
• WHO/ECOG performance status of 0 or 1 with no deterioration (that is, ECOG PS>1) over the previous 2 weeks prior to day of first dosing
• Has measurable disease per modified RECIST1.1
• Has adequate bone marrow reserve and organ function at baseline

Ausschlusskriterien
• As judged by the investigator, any condition that would interfere with evaluation of the investigational product or interpretation of participant safety or study results.
• Active or prior documented autoimmune or inflammatory disorders
• History of another primary malignancy with exceptions.
• Uncontrolled intercurrent illness
• Tuberculosis, hepatitis B (HBV) or hepatitis C (HCV), human immunodeficiency virus (HIV) infection that is not well controlled
• Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment
• Untreated or progressive CNS metastatic disease

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Mesotheliom

Medizinischer Befund
Unresectable Pleural Mesothelioma

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Stefan Kasper-Virchow

+49 (0) 201 723-2040
stefan.kasper-virchow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Charité - Universitätsmedizin Berlin

Einschlusskriterien
1. Patient’s signed informed consent.
2. Patient’s age ?18 years at the time of signing the informed consent.
3. Histologically confirmed adenocarcinoma of the colon or rectum.
4. Resected (R0 or R1) and/or effectively treated metastases (all techniques allowed) of colorectal cancer within 3-10 weeks before randomization AND resected primary tumor (synchronous or metachronous).
5. Absence of significant active wound healing complications (if applicable) prior to randomization. Resolved wound healing complications after resection/ablation are acceptable for inclusion into the trial.
6. No radiographic evidence of active metastatic disease at study entry in a CT and/or MRI scan not older than 8 weeks. Pre-surgery/ablation images are eligible for the study if all lesions have been addressed in the interval.
7. ECOG performance status 0-2.
8. Adequate bone marrow, hepatic and renal organ function, defined by the following laboratory test results:
• Absolute neutrophil count ? 1.5 x 109/L (1500/µL)
• Hemoglobin ? 80 g/L (8 g/dL)
• Platelet count ? 100 x109/L (100000/µL) without transfusion
• Total serum bilirubin of ? 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST/GOT) ? 3.0 × ULN.
• Calculated glomerular filtration rate (GFR) according to Cockcroft-Gault formula or according to MDRD ? 50 mL/min or serum creatinine ? 1.5 x ULN
9. Patients without anticoagulation need to present with an INR < 1.5 x ULN and PTT < 1.5 x ULN. Patient with prophylactic or therapeutic anticoagulation are allowed into the trial.
10. Proficient fluorouracil metabolism as defined:
a) Prior treatment with 5-FU or capecitabine without unusal toxicity
or
b) If tested, normal DPD deficiency test according to the standard of the study site
or
c) If tested, in patients with DPD deficiency test with a CPIC activity score of 1.0-1.5 fluoropyrimidine dosage should be reduced by 50%
11. For women of childbearing potential (WOCBP): negative pregnancy test within 14 days before randomization and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study treatment.
A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (? 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male partner’s sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
For men: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment. Men must refrain from donating sperm during this same period.
With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of study medication to avoid exposing the embryo.

Ausschlusskriterien
1. Treatment of metastases greater than 3 cm with radio-frequency/microwave ablation within 24 months prior to study entry if applicable.
2. Treatment of metastases greater than 5 cm with radiation (stereotactic/ brachytherapy) within 24 months prior to study entry if applicable.
3. Previous chemotherapy for metastatic or localized disease with > 6 cycles of FOLFOX (or FOLFOXIRI) or > 4 cycles of CAPOX/XELOX.
4. New York Heart Association Class III or greater heart failure by clinical judgement.
5. Myocardial infarction within 6 months prior to randomization; percutaneous transluminal coronary angioplasty (PTCA) with or without stenting within 6 months prior to randomization.
6. Unstable angina pectoris.
7. Unstable cardiac arrhythmia > grade 2 NCI CTCAE despite anti-arrhythmic therapy.
8. Ongoing toxicities > grade 2 NCI CTCAE, in particular peripheral neuropathy.
9. Active uncontrolled infection by investigator’s perspective.
10. Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
11. Known hypersensitivity to 5-FU, leucovorin, irinotecan or oxaliplatin or to any of the other excipients listed in section 6.1 of the corresponding SmPC.
12. Bone marrow depression after radio- or chemotherapy.
13. Severe kidney dysfunction (creatinine clearance < 30 ml/min) or changes in blood count.
14. Recent or concomitant treatment with brivudine.
15. Peripheral sensitive neuropathy with functional impairment (> grade 1 acc. to CTCAE version 5.0 (see appendix)).
16. Inflammatory bowel disease and/or bowel obstruction.
17. Simultaneous application of Johannis herbs preparations.
18. Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.
19. If tested, DPD deficiency test with a CPIC activity score <1.
20. Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to randomization, or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 21 days prior to randomization or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure.
21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
22. Medical history of malignant disease other than mCRC with the following exceptions:
- patients who have been disease-free for at least three years before randomization
- patients with adequately treated and completely resected basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine cancer
- patients with any treated or untreated malignant disease that is associated with a 5-year survival prognosis of ? 90% and does not require active therapy
23. Known alcohol or drug abuse.
24. Pregnant or breastfeeding females.
25. Participation in a clinical trial or experimental drug treatment within 28 days prior to potential inclusion in the clinical trial or within a period of 5 half-lives of the substances administered in a clinical trial or during an experimental drug treatment prior to potential inclusion in the clinical trial, depending on which period is longest, or simultaneous participation in another clinical trial while taking part in this clinical trial.
26. Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
27. Limited legal capacity.

Geschlecht
Männlich, Weiblich

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
Metastatic colorectal cancer after definite interventional therapy of all lesions

MedDRA Term
Metastatic colorectal cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Stefan Kasper-Virchow

+49 (0) 201 723-2040
stefan.kasper-virchow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Daiichi Sankyo Inc., USA

Einschlusskriterien
* Sign and date the informed consent form prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
* Participants aged =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
* Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:

Cutaneous (acral and non-acral) melanoma
* Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma
* Disease progression while on or after having received treatment with =1 prior line of anti-programmed cell death protein (PD-1) or anti-programmed death-ligand 1 (PD-L1) based therapy (previous use of other immune checkpoint inhibitors [ICIs] [ie, anti-CTLA4, anti- LAG-3] is acceptable). Prior anti-PD-(L)1 therapy in the adjuvant setting is allowed if there is recurrence within 12 weeks of the last dose. If the participant had BRAFm melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.

Squamous cell carcinomas of the head and neck
* Squamous cell carcinoma of the head and neck (with a primary location of oral cavity,oropharynx, larynx, hypopharynx) that is human papillomavirus (HPV) positive or negative (as determined by local standard). Excludes tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
* Disease progression after having received treatment with =1 and <3 prior lines of systemic therapy in the unresectable recurrent or metastatic setting.
* Must have had disease progression on anti-PD-(L)1 (either as monotherapy or in combination with chemotherapy or other therapies). Must also have had disease progression on a platinum-based chemotherapy (PBC) regimen either in the recurrent or metastatic setting or in the locally advanced setting with curative intent.

Gastric or GEJ adenocarcinoma
* Tumor tissue must be confirmed as negative for HER2 expression (immunohistochemistry [IHC] 0/1+ or IHC 2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
* Disease progression after having received treatment with =2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.

Ovarian Carcinoma
* Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
* Documented disease progression =4 weeks after the last dose of PBC and <6 months of last dose of PBC in the advanced or metastatic setting. Prior use of folate reductase alpha targeting antibody-drug conjugate (ADC) (ie, mirvetuximab soravtansine) is allowed.

Cervical Cancer
* Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.
* Disease progression after having received =1 line of systemic therapy in the recurrent or metastatic setting. This may include prior anti-PD-(L)1 treatment and/or tissue factor directed ADC (tisotumab vedotin [TV]) per regional standard of care.

Endometrial Cancer
* Pathologically or cytologically documented endometrial cancer (carcinoma of any histological sub-type or endometrial carcinosarcoma), irrespective of microsatellite instability (MSI) or mismatch repair (MMR) status.
* Documented disease progression after having received =1 prior line of therapy (maximum of 3) PBC containing systemic treatment and an anti-PD(L)-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

Bladder Cancer
* Pathologically or cytologically documented locally advanced/unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.
* Relapsed or progressed after treatment with =1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting. At least 1 line of therapy must also contain one of the following treatment modalities: chemotherapy or enfortumab vedotin. Prior fibroblast growth factor receptor (FGFR)-inhibitor treatment for those who are eligible are allowed.
- Required treatments can be given in combination or sequentially
- Prior cisplatin-based therapy or PD-(L)1 inhibitor therapy given for the treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy
- The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy
- A minimum of 20 subjects in the second-line setting who have previously received enfortumab vedotin and pembrolizumab in combination will be enrolled.

Esophageal Carcinoma
* Pathologically or cytologically documented esophageal squamous cell carcinoma.
* Must have documented disease progression after having received 2 prior lines of therapy including previous PBC with or without an anti-PD-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

Pancreatic Carcinoma
* Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.
* Relapsed or disease progression after having received 1 prior line of systemic therapy in the locally advanced/metastatic setting.

Prostate Cancer
* Pathologically or cytologically documented unresectable locally advanced or metastatic castration-resistant prostate cancer (CRPC).
* Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
* Surgically or medically castrated, with testosterone levels of <50 ng/dL.
* Documented objective progression as determined by radiographic progression for subjects with measurable disease after androgen deprivation.
* Relapsed or disease progression after having received treatment with =1 of the following novel hormonal agents: abiraterone, enzalutamide, apalutamide, or darolutamide.
* Relapsed or disease progression after having received =1 cytotoxic chemotherapy regimen that included a taxane.

* Has =1 measurable lesion on CT or MRI as per RECIST v1.1 by investigator assessment. Prostate cancer participants with bone only disease may be eligible.
* Provides a pretreatment tumor tissue sample of sufficient quantity, as defined in the Study Laboratory Manual. The following tissue samples can be provided as the pretreatment tumor tissue sample:
- Tissue collected from a biopsy (from =1 lesion not previously irradiated) performed since progression while on or after treatment with the most recent systemic cancer therapy regimen and prior to signing of the tissue ICF

OR

- Pretreatment tumor biopsy from =1 lesion not previously irradiated and amenable to sampling after signing of the tissue ICF. The pretreatment tissue requirement may be waived after discussion and agreement with the Sponsor.

* Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at screening.

Ausschlusskriterien
* Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
* Has nasopharyngeal cancer.
* Has mucosal or uveal melanoma.
* Has a history of (non-infectious) interstitial lung disease (ILD), that required corticosteroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses
* Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1.
* Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
* Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
* Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:
- Adequately treated nonmelanoma skin cancer
- Adequately treated intraepithelial carcinoma of the cervix
- Any other curatively treated in situ disease
* Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator's opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol
* Has previously received irinotecan treatment in the advanced or metastatic disease setting.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Solide Tumoren

Medizinischer Befund
Advanced Solid Tumor\nMelanoma\nHead and Neck Cancer\nGastric Cancer\nOvarian Carcinoma\nCervical Cancer\nEndometrial Cancer\nBladder Cancer\nEsophageal Cancer\nPancreatic Carcinoma\nProstate Cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Sebastian Bauer

sebastian.bauer@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

IDRx, Inc

info@IDRX.COM

Einschlusskriterien
Phase 1
1. Male or female participants ≥18 years of age
2. Histologically or cytologically confirmed metastatic and/or surgically unresectable GIST
3. Documented progression on imatinib (Phase 1)
4. Documented pathogenic mutation in KIT OR any PDGFRA mutation other than exon 18 mutations, determined through local testing
5. At least one measurable lesion by mRECIST v1.1 for participants with GIST
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Resolution of any toxicities from prior treatment(s) to ≤ Grade 1 by NCI CTCAE v5.0 criteria, or have resolved to baseline, at the time of first dose of study drug.
8. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.

Additional for Phase 1b Exploratory Cohorts
1. For Cohort 1, progressed on imatinib only (second line therapy)
2. For Cohort 2, progressed on both imatinib and sunitinib (third line therapy) or progressed on imatinib, sunitinib, and an additional agent (i.e., regorafenib or ripretinib) (fourth line therapy)
3. For Cohort 3, progressed on at all U.S. -approved TKI therapies for KIT-mutant GIST [imatinib, sunitinib, regorafenib, and ripretinib] (fifth line or greater therapy)

Ausschlusskriterien
1. Any prior exposure to the following investigational agents NB003 or THE-630 or bezuclastinib plus sunitinib combination.
2. GIST with no documented mutation in both KIT and PDGFRA genes.
3. Any prior primary CNS malignancy or known untreated or active central nervous system metastases.
4. Has an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics.
5. Has significant, uncontrolled, or active cardiovascular disease.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
GIST - Gastrointestinaler Stromatumor

Medizinischer Befund
Gastrointestinal Stromal Tumor (GIST)\nDigestive System Disease\nGastrointestinal Diseases\nMetastatic Cancer

MedDRA Term
Gastrointestinal stromal tumour, Gastrointestinal stromal tumor

Institute
Innere Klinik (Tumorforschung), Klinik für Kinderheilkunde III, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. Uta Dirksen

+49 (0)201 723-82025
uta.dirksen@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

German Pediatric Oncology Group, GPOH gGmbH, Berlin

Einschlusskriterien
•Histologically (and molecularly) diagnosed primary localised (SR) or metastatic (HR) Ewing sarcoma or so called Ewing-like sarcoma ( i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue; pathological diagnosis can be performed at the investigational site
•Any sex, age >2 and < 50 years by the date of diagnostic biopsy
•Informed consent must be obtained according to national and GCP guidelines and signed prior to trial entry. Subjects and when applicable parental or legal representative(s) must understand and voluntarily provide permission to the ICF, prior to conducting any trial-related assessments / procedures. Willingness and ability to comply with scheduled visits and trial procedures are required.
•White blood cell (WBC) count > 2000/µl*
•Assessment of cardiac function including LVEF > 40% and SF > 28%*
•Serum creatinine < 1.5 X ULN*
•For patients of childbearing potential, a negative pregnancy test must be documented prior to enrolment and repeated every month during therapy. Female and male patients, who are fertile and sexually active, must agree to use an effective form of contraception from the time of signing the ICF until 6 months after the end of treatment.
*Parameters must be checked within the screening phase of 45 days from biopsy biopsy / surgery and after diagnosis of metastatic disease to registration.

Ausschlusskriterien
•Treatment of more than one cycle of chemotherapy prior to registration in the SR group
•Concurrent treatment within any other clinical trials, excluding trials with different endpoints, which, due to the nature of their endpoints, must run parallel to iEuroEwing trial, e.g. studies on antiemetics, antimycotics, antibiotics, strategies for psychosocial support, etc.
•Clinically significant and uncontrolled, or active cardiac disease
•Evidence of invasive fungal infection or other severe systemic infection requiring systemic / parenteral therapy
•Hypersensitivity to the active substance or other excipients contained in the investigational medical products listed in the summary of product characteristics (SmPC) or investigators brochure (IB).
•Secondary malignancy
•Pregnancy or lactation
•Female and male subjects with child-bearing potential, who avoid using highly effective contraceptive methods
•Any other medical, psychiatric, or social condition which is incompatible with the protocol treatment
•Contraindications according to the respective applicable SmPCs

Additional exclusion criteria iEuroEwing-SR-RT part:
•Primary diagnosed and histologically confirmed metastatic (HR) Ewing sarcoma or Ewing-like sarcoma of bone and/or soft tissue
•Patients who receive preoperative RTX
•Patients who receive Brachytherapy
•Patients who have been diagnosed with pleural effusion
•Patients with previous RT in the same region

Studienteilnehmende Mindestalter
12 Jahr(e)

Studienteilnehmende Höchstalter
64 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
KIK-Onko

Medizinischer Befund
Ewing Sarcoma

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Martin Schuler

martin.schuler@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Eli Lilly & Company, USA

Einschlusskriterien
• Have Histological or cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Have evidence of KRAS G12D mutation in tumor tissue or circulating tumor DNA
• Have an ECOG performance status of = 1
• Must have received = 1 prior line of systemic chemotherapy for advanced or metastatic disease
• Participants with asymptomatic or treated CNS disease may be eligible.

Ausschlusskriterien
• Have known active CNS metastases and/or carcinomatous meningitis.
• Have any unresolved toxicities from prior therapy greater than National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 1.
• Have significant cardiovascular disease as unstable angina or acute coronary syndrome, history of myocardial infarction, known reduced left ventricular ejection fraction.
• Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
• Have known active hepatitis B virus (HBV) and hepatitis C virus (HCV).
• Have other active malignancy unless in remission with life expectancy greater than (>) 2 years.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Solide Tumoren

Medizinischer Befund
KRAS G12D-mutant solid tumors

MedDRA Term
Solid tumor

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Michael Pogorzelski

michael.pogorzelski@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Merus N.V.

Einschlusskriterien
• Signed ICF before initiation of any study procedures.
• Age = 18 years at signing of ICF.
• Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
• HNSCC patients progressed on or after anti-PD-1 therapy and platinum-containing therapy.
• The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
• Documentation of p16 status (positive or negative) by local laboratory IHC for patients with primary oropharyngeal cancer.
• A baseline new tumor sample unless the patient has an available tumor sample as an FFPE block with sufficient material.
• Measurable disease as defined by RECIST v1.1 by radiologic methods.
• ECOG PS of 0 or 1
• Life expectancy = 12 weeks, as per investigator
• Adequate organ function (as per protocol)

Ausschlusskriterien
• Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
• Known leptomeningeal involvement
• Any systemic anticancer therapy within 4 weeks of the first dose of study treatment.
• Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
• Persistent Grade >1 clinically significant toxicities related to prior antineoplastic therapies
• History of hypersensitivity reaction to any of the excipients of treatment required for this study.
• Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment or history of myocardial infarction within 6 months of study entry
• History of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease
• Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy
• Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
• Patients with known infectious diseases (as per protocol)
• Pregnant or breastfeeding patients
• Patient has a primary tumor site of nasopharynx (any histology).

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Kopf-Hals-Tumore

Medizinischer Befund
Head and Neck Squamous Cell Carcinoma

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Jens Siveke

jens.siveke@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

AIO-Studien-gGmbH, Berlin

Einschlusskriterien
- Age = 18 years and = 75 years; histologically confirmed metastatic adenocarcinoma of the pancreas;
- medical and technical operability of the primary tumor defined tumor board assessment;
- limited metastatic status (= 3 resectable liver metastases);
- adequate hematological (WBC =3000/µL, absolute neutrophil count =1500 /µL, platelets =100.000/µL, hemoglobin =8 g/dL), hepatic (bilirubin =2.5 x mg/dl) and renal function (creatinine clearance >50ml/min) parameters;
- ECOG performance status = 1;
- signed study-specific consent form prior to therapy;
- measurable disease according to RECIST v1.1.

Ausschlusskriterien
- Unresectable pancreatic cancer;
- prior chemotherapy within 6 months or prior radiation therapy within 28 days;
- significant comorbidity (e.g. cardiovascular, pulmonary);
- peritoneal carcinomatosis or > three liver metastases or nonextrahepatic metastasis;
- inability to understand the study and/or comply with the protocol procedures.

Studienteilnehmende Mindestalter
18 Jahr(e)

Studienteilnehmende Höchstalter
75 Jahr(e)

Indikation
Tumoren der Leber und Bauchspeicheldrüse und der Gallenwege

Medizinischer Befund
Locally resectable but oligometastatic pancreatic cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum, Nationales Centrum für Tumorerkrankungen West

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Sebastian Bauer

sebastian.bauer@uk-essen.de

Hufelandstr. 55
45147 Essen

Einschlusskriterien
- Patienten mit fortgeschrittenen Tumorerkrankungen
- Keine kurative Therapieoption
- Karnofsky Index mind. 70%
- Indikation für eine geeignete Tumorbiopsie

Geschlecht
Divers, Männlich, Weiblich

Indikation
Diverse Tumorerkrankungen

Medizinischer Befund
Tumor Research

Institute
Innere Klinik (Tumorforschung), Ruhrlandklinik - Klinik für Thoraxchirurgie und thorakale Endoskopie, Ruhrlandklinik - Klinik für Thoraxchirurgie und thorakale Endoskopie, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Martin Schuler

martin.schuler@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinik Essen (AöR)

+49 (0)201 723-0
info@uk-essen.de

Hufelandstraße 55
45147 Essen

Einschlusskriterien
1. Patients with histologically (core biopsy) or cytologically (e.g., bronchoscopy-guided biopsy) confirmed non-small-cell lung cancer (NSCLC) eligible for anatomic resection, with the following specifications:
o Clinical stages I B, II or selected stage III A (T3 N1, T4 with satellite nodule in the same lung N0/N1, selected T1a-T2b N2 cases considered suitable for primary surgical approach by the multidisciplinary tumor board) according to UICC 8th edition
o Confirmation of an oncogenic EGFR mutation (EGFR p.L858R, EGFR exon 19 in-frame deletion, EGFR exon 20 in-frame insertions, EGFR p.S768I, EGFR p.L861Q, EGFR p.G719x - additional EGFR mutations with clinically validated oncogenicity and susceptibility to amivantamab may be eligible following discussion and approval by the coordinating investigator in his capacity as sponsor representative) by validated assaytechnology (e.g., diagnostic NGS or PCR-based genotyping, adhering to quality standards defined by the nNGM Lung Cancer biomarker standard operating procedure (version 007 or higher) in Germany, or equivalent in Belgium and the Netherlands) in a pretreatment biopsy (primary tumor or lymph node metastasis)
2. Males and females, ages >= 18 years, inclusive
o A participant of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study treatment and must agree to further serum or urine pregnancy testing during the study.
o A participant must be (as defined in Appendix IV: Contraceptive Guidance and Collection of Pregnancy Information) either of the following:
? Not of childbearing potential
? Of child-bearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of study treatment is given
? Of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method (examples of highly effective methods of contraception are located in Appendix IV: Contraceptive Guidance and Collection of Pregnancy Information).Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.
? Note: If the childbearing potential changes after start of the study (e.g., participant of childbearing potential who is not heterosexually active becomes active, premenarchal participant experiences menarche) the participant must begin birth control, as described above
o A participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
o A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A participant who is sexually active with a partner of childbearing potential must agree to use a condom with spermicidal foam/gel/film/cream/suppository and their partner must also be practicing a highly effective method of contraception (i.e., established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]). If the participant is vasectomized, they must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but their partner is not required to use contraception.
o A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.
o Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
3. ECOG performance status = 1
4. Exclusion of extensive mediastinal lymph node metastases (multilevel N2, N3) by PET/CT and/or invasive mediastinal lymph node staging by EBUS-TBNA and/or staging mediastinoscopy as performed by institutional guidelines.
5. Exclusion of distant metastases by standard of care imaging studies, which include but are not limited to PET/CT or PET/MRI, or CT or MRI of thorax, abdomen including pelvic region, and bone scan. Asymptomatic brain metastases will be excluded by MRI or contrastenhanced CT as indicated by institutional guidelines and patient factors.
6. Measurable target tumor (pre RECIST 1.1) prior to preoperative study therapy using standard imaging techniques.
7. Sufficient pulmonary function (ppFEV1>30%, ppDLCO>30%) to undergo curative lung cancer surgery. Exercise tests should be performed in all patients with FEV1 or DLCO 75% predicted or >20 mL·kg-1·min-1 qualify for pneumonectomy; <35% predicted or <10 mL·kg-1·min-1 indicate high risk for any resection. There is insufficient evidence to recommend specific cut-off values for lobectomy or segmentectomy.
8. Adequate hematological, hepatic and renal function parameters:
o Leukocytes = 2,000/mm³, platelets = 100,000/mm³, absolute neutrophil count (ANC) = 1,500/µL, hemoglobin = 9 g/dL (stage 1) or 10 g/dL (stage 2)
o Anti-platelet therapy (such as but not limited to clopidogrel) should be discontinued pre-operatively according to local standards. If this therapy cannot be interrupted due to severe cardiovascular comorbidity, patient is ineligible for the trial
o Adequate coagulation function as defined by International Normalized Ratio (INR) = 1.5, and a partial thromboplastin time (PTT) = 5 seconds above the upper limit of normal (ULN) (unless receiving anticoagulation therapy). Patients receiving warfarin/phenprocoumon or direct oral anticoagulants are to be bridged according to local standards and have achieved stable coagulation profile prior to surgery
o Serum creatinine = 1.5 x upper limit of normal and creatinine clearance >45 mL/min as measured or calculated by Cockcroft- Gault formula for estimated creatinine clearance (Appendix VII)
o Bilirubin = 1.5 x upper limit of normal, AST and ALT = 3.0 x upper limit of normal, alkaline phosphatase = 6 x upper limit of normal. Subjects with Gilbert's syndrome can be enrolled if conjugated bilirubin is within normal limits
9. Sufficient cardiac left ventricular defined as LVEF = 50% documented either by echocardiography or MUGA (echocardiography preferred, MUGA not used in German sites) within 6 months before first administration of study drug.
10. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.

Ausschlusskriterien
1. Lung cancer entity and stage other than defined by the inclusion criteria.
2. Absence of a predictive oncogenic EGFR mutation (EGFR p.L858R, EGFR exon 19 in-frame deletion, EGFR exon 20 in-frame insertions, EGFR p.S768I, EGFR p.L861Q, EGFR p.G719x - additional EGFR mutations with clinically validated oncogenicity and susceptibility to amivantamab may be eligible following discussion and approval by the coordinating investigator in his capacity as sponsor representative) in apretreatment biopsy (primary tumor or metastasis).
3. Active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug- or radiation-induced ILD/pneumonitis.
4. Subjects with a condition requiring continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted.
5. Subjects who have undergone organ transplant or allogeneic stem cell transplantation.
6. ppFEV1<30%, ppDLCO<30%, ppVO2max < 10 ml/min/kg or other criteria of functional inoperability per local guidelines.
7. History of uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
o Myocardial infarction (MI), NSTEMI, coronary artery bypass grafting, or stroke/transient ischemic attack (TIA) within the 6 months prior to consent
o Uncontrolled angina within the 3 months prior to consent
o Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
o Prolonged corrected QTc interval by Fridericia's > 470 msec
o Uncontrolled persistent hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg)
o Clinically significant deep vein thrombosis or pulmonary embolism within 1 month prior to study treatment (clinically nonsignificant thrombosis or incidental, asymptomatic pulmonary embolism are not exclusionary)
o Pulmonary hypertension (sPAP >35 mmHg; only measured if clinically indicated and/or mandated per local guidelines)
8. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion etc.).
9. Cardiovascular or pulmonary disease-related requirement for daily supplemental oxygen.
10. History of two or more myocardial infarctions or two or more coronary revascularization procedures.
11. Patients with active neurological disease should be excluded.
12. Active malignancy or a prior malignancy within the past 3 years. Patients with the following conditions are not excluded from participation:
o Patients with adequately resected skin cancer (melanoma or non-melanoma), cervical carcinoma in-situ, intestinal polyps not containing invasive cancer, treated breast carcinoma in-situ or bladder carcinoma in-situ that are considered completely cured, and patients with isolated elevation in prostate-specific antigen or low risk prostate cancer managed with active surveillance or watchful waiting in the absence of radiographic evidence of metastatic prostate cancer.
13. Known history of positive test for human immunodeficiency virus (HIV- 1 and HIV-2) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV-1 and HIV-2 must be performed at screening.
14. Positive test result for hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg).
o Note: participants with a prior history of HBV demonstrated by positive hepatitis B core antibody are eligible if they have at screening (i) a negative HBsAg and (ii) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.
15. Positive hepatitis C antibody (anti-HCV).
o Note: participants with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.
16. History of other clinically active infectious liver disease
17. Uncontrolled diabetes mellitus
18. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection.
19. Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements.
20. Any ophthalmologic condition that is clinically unstable.
21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of amivantamab, carboplatin or pemetrexed, or may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
22. Receipt of live attenuated vaccine within 30 days prior to the first dose of study medication.
23. Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment
24. The patient has undergone major surgery within 28 days prior to enrollment except staging mediastinoscopy, diagnostic VATS or implantation of a venous port-system, or has not recovered from prior surgery.
25. Any other concurrent preoperative antineoplastic treatment including irradiation
26. Pregnant women
27. Breastfeeding women
28. Insufficient cardiac left ventricular function defined as LVEF<50% by echocardiography (outside Germany: or MUGA scan)
29. A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
30. Subjects with history of severe or life-threatining (grade 3 or 4) infusion-related reactions to prior antibody therapy or immune therapy
31. Prior treatment with amivantamab or any EGFR tyrosine kinase inhibitor
32. Participation in another interventional clinical study within the last 3 months prior to inclusion or simultaneous participation in other interventional clinical studies
33. Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety.
34. Any contraindications against amivantamab (stages 1 and 2), carboplatin or pemetrexed (stage 2)

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Non-small-cell lung cancer stages I B, II and selected stages III A with oncogenic EGFR mutation

Institute
Innere Klinik (Tumorforschung), Klinik für Kinderheilkunde III, Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Stefan Schönberger

stefan.schoenberger@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Universitätsklinikum Aachen

Einschlusskriterien
- Histologisch bestätigtes, neu diagnostiziertes NPC bei Patienten ab 3 bis 17 Jahren oder Histologisch bestätigtes, neu diagnostiziertes NPC bei Patienten ab 18 Jahren, EBV positiv, WHO Stadium II, III
- AJCC Stadium ≥ II (Kinder), ≥ III (Erwachsene)
- Messbare Erkrankung per MRT via RECIST 1.1
- Ausreichendes Tumorgewebe für Referenz und PD L1 Staining
- Vorliegen einer Einwilligungserklärung

Ausschlusskriterien
- NPC Stadium I, Rezidiv oder NPC als Sekundärmalignom
- Vorherige Chemotherapie oder Radiotherapie
- Vorliegen einer weiteren aktiven malignen Erkrankung
- Vorherige Behandlung mit einem anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 Antikörper oder einem anderen Antikörper oder Medikament, das die T-Zell-Co-Stimulation oder Checkpoint-pathways anspricht
- Erhalt eines anderen Studienmedikaments bis zu 30 Tage vor Einschluss in diese Studie
- Vorliegen einer aktiven, bekannten Autoimmunerkrankung
- Systemische Behandlung mit Kortikosteroiden (größer 10 mg tägliches Prednison Äquivalent) oder Immunsuppressiva innerhalb von 14 Tagen vor Start der Studienmedikation.
- Nachweis einer akuten oder chronischen Hepatitis B oder Hepatitis C
- Nachweis einer HIV-Infektion
- Unzureichende hämatologische, renale oder hepatische Funktion
- Hörverlust von mehr als 20dB bei 3kHz
- Bekannte Allergie oder Hypersensibilität gegen ein Studienmedikament
- Vorliegen einer anderen Erkrankung, die nach Meinung des Investigators ein nicht akkzeptables Risiko für den/die Teilnehmende bedeuten würde,
- Vorliegen einer Schwangerschaft oder stillende Frauen; sexuell aktive Teilnehmende müssen einverstanden sein, eine ausreichende Kontrazeption vorzunehmen.

Studienteilnehmende Mindestalter
3 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
KIK-Onko

Medizinischer Befund
EBV positives Nasopharynx Karzinom

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Stefan Kasper-Virchow

+49 (0) 201 723-2040
stefan.kasper-virchow@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Janssen Research & Development, LLC

Einschlusskriterien
• Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
• Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
• Must agree to the submission of fresh tumor tissue
• Have measurable disease according to RECIST v1.1
• Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1

Ausschlusskriterien
• Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
• Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
• Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
• Has prior exposure to any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Tumoren des Magen-Darm-Traktes

Medizinischer Befund
KRAS\/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

MedDRA Term
Colorectal cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Michael Pogorzelski

michael.pogorzelski@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Janssen Research & Development, LLC

Einschlusskriterien
* Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies. Acceptable prior lines of therapy will be determined according to specific cohort: (a) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (b) Any known p16 status of tumor must be negative (Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing); (c) Participants must provide local testing results of programmed cell death ligand 1 (PD-L1) status, if available
* Participants in Cohorts 1, 2, and 3B must have measurable disease according to RECIST version 1.1. Participants in Cohort 3A must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1
* Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except for alopecia or post-radiation skin changes [any grade], Grade less than or equal to [<=]2 peripheral neuropathy and Grade <=2 hypothyroidism stable on hormone replacement)
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor within 7 days prior to the date of the laboratory test.
* Participants should have:
a) Hemoglobin >=9 grams per deciliter (g/dL)
b) Neutrophils >=1.5 x 10^3/mcg
c) Platelets >=100 x 10^3/mcg

Ausschlusskriterien
* Uncontrolled illness including any medical history or current (non-infectious) interstitial lung disease (ILD)/ pneumonitis/ pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Participant with untreated brain metastases leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
* Participant with a history of clinically significant cardiovascular disease
* Received prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study treatment. The maximum required washout is 28 days
* Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Kopf-Hals-Tumore

Medizinischer Befund
Recurrent\/Metastatic Head and Neck Squarnous Cell Carcinoma

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Halime Kalkavan

halime.kalkavan@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Ose Immunotherapeutics

Einschlusskriterien
1. Male or female, aged = 18 years
2. Patients expressing HLA-A2 phenotype in blood by pre-screening central laboratory
3. Patients with histologically or cytologically squamous or non-squamous documented NSCLC, metastatic stage at study entry, not eligible for definite surgery or radiation, without EGFR, ALK and ROS1 gene alterations eligible for targeted therapy; other sensitizing mutations known to be immunosensitive are eligible in case of lack of local access to targeted therapy (i.e.; KRAS G12C and BRAF mutations) after Sponsor's agreement
4. Patients with secondary resistance to ICI;

Other inclusion and exclusion criteria will apply per protocol.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
HLA-A2 positive phenotype and metastatic Non-Small Cell Lung Cancer

MedDRA Term
Squamous non-small cell lung cancer, Lung cancer non-small cell stage IV, Non-squamous non-small cell lung cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

PMV Pharmaceuticals, Inc

Einschlusskriterien
- At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available
- Advanced solid malignancy with a TP53 Y220C mutation
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Previously treated with one or more lines of anticancer therapy and progressive disease
- Adequate organ function
Additional Criteria for Inclusion in Phase 1b (PC14586 + pembrolizumab combination)
- Anti-PD-1/PD-L1 naive or must have progressed on treatment
- Measurable disease

Ausschlusskriterien
- Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
- Radiotherapy within 28 days of receiving the study drug
- Primary CNS tumor (Phase 1, Phase 2 Cohort A)
- History of leptomeningeal disease or spinal cord compression
- Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptom
- Stroke or transient ischemic attack within 6 months prior to screening
- Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities
- Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors
- History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
- History of prior organ transplant
- Known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
- Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection
Additional Criteria for Exclusion from Phase 1b (PC14586 + pembrolizumab combination)
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE).
- Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
- Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug.
- Hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- History of radiation pneumonitis.
- History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
- Active infection requiring systemic therapy.
- Known history of HIV infection.

Studienteilnehmende Mindestalter
12 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Lungenkrebs, Brustkrebs, Kopf-Hals-Tumore, Tumoren des Magen-Darm-Traktes, Urogenitale Tumore, Solide Tumoren, Gynäkologische Tumore, Diverse Tumorerkrankungen

Medizinischer Befund
Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation\n\nAdvanced Solid Tumor\nAdvanced Malignant Neoplasm\nMetastatic Cancer\nMetastatic Solid Tumor\nLung Cancer\nOvarian Cancer\nEndometrial Cancer\nProstate Cancer\nColorectal Cancer\nBreast Cancer\nOther Cancer\nLocally Advanced Head and Neck Cancer

MedDRA Term
Ovarian cancer, Lung cancer, Breast cancer, Solid tumor, Endometrial cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Martin Schuler

martin.schuler@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Revolution Medicines, Inc.

Einschlusskriterien
• At least 18 years old and has provided informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed NSCLC, either locally advanced or metastatic, not amenable to curative surgery or radiotherapy.
• Measurable disease per RECIST v1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation).
• One to two prior lines of therapy including an anti-PD-1/anti-PD(L)-1 agent and platinum-based chemotherapy.
• Documented RAS mutation status, defined as Nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
• Able to take oral medications.

Ausschlusskriterien
• Prior therapy with direct RAS-targeted therapy or docetaxel.
• Untreated central nervous system (CNS) metastases.
• Medically significant comorbidities (significant cardiovascular disease, lung disease, or impaired GI function).
• Ongoing anticancer therapy.
• Pregnancy and/or breastfeeding.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Non Small Cell Lung Cancer (NSCLC)

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Anja Welt

anja.welt@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

F. Hoffmann-La Roche AG

Einschlusskriterien
Stage 1
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Metastatic or inoperable locally advanced, histologically documented TNBC
- For patients in the 1L PD-L1 positive cohort: no prior systemic treatment for metastatic or inoperable locally advanced TNBC
- For patients in the 2L CIT-naïve cohort: Eligible for capecitabine monotherapy
- For patients in the 2L CIT-naïve cohort: Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy (chemo) for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer
- Life expectancy>= 3 months
- Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1and/or additional biomarker status via central testing
- For patients in the 1L PD-L1 positive cohort: positive PD-L1 expression, defined as >= 1%of the tumor area occupied by PD-L1- expressing tumor-infiltrating immune cells of any intensity Stage 1 and Stage 2
- Measurable disease according to Response Evaluation Criteria in Solid Tumors 1.1
- Tumor accessible for biopsy
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to initiation of study treatment
- Negative HIV test, hepatitis B surface antigen at screening, and hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL at screening
- For women of childbearing potential: agreement to remain abstinent or use treatment arm-specific contraceptive measures and agreement to refrain from breastfeeding and donating eggs
- For men: agreement to remain abstinent or use treatment arm- specific contraceptive measures, and agreement to refrain from donating sperm for a treatment arm-specific time period Stage 2
- ECOG Performance Status of 0, 1, or 2
- Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment
- Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab (Atezo), disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
- Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1

Ausschlusskriterien
Stage 1
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies
- Treatment with investigational therapy within 28 days prior to C1D1
- Biologic treatment or other systemic treatment within 2 weeks (wks) prior to C1D1
- Eligibility only for the control arm Stage 1 (2L CIT naïve cohort only)
- Prior treatment with capecitabine
Stage 1, 2
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, tumor-related pain and uncontrolled or symptomatic hypercalcemia
- Symptomatic, untreated, or actively progressing central nervous system metastases.
- History of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis or tuberculosis on screening and malignancy other than breast cancer within 2 years prior to screening.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- History of autoimmune disease or immune deficiency
- Grade >= 3 hemorrhage or bleeding event within 28 days prior to
C1D1
- Severe infection within 4 wks prior C1D1
- Major surgical procedure within 4wks
- Treatment with antibiotics or live, attenuated vaccine within 2 wks or 4wks prior to C1D1 respectively
- Treatment with systemic immunostimulatory agents within 4wks or 5 half-lives of the drug prior to C1D1
- Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at the time of consent Ipatasertib (Ipat) - Containing arm (Stage 1)
- Prior treatment with ipat or other Akt inhibitors
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia
- History of Type I or Type II diabetes mellitus requiring insulin
- Congenital long QT syndrome or screening QT interval corrected through use of Fridericia's formula > 480ms
- Treatment with strong CYP3A4 inducers or inhibitors within 2wks or 5 drug-elimination half-lives prior to C1D1. SGN-LIV1A - Containing arm (Stage 1)
- Prior treatment with SGN-LIV1A or MMAE -based biologic
- Grade>= 2 neuropathy
- Radiotherapy within 2wks prior to C1D1
- AST/ALT > 1.5 x ULN, or 3 x ULN if liver metastases present
- Documented history of a cerebrovascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure, within 6 months prior to study enrollment. Bevacizumab (Bev) - Containing arm (Stage 1)
- Inadequately controlled arterial hypertension
- History of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease within 6 months prior to C1D1
- History of hemoptysis within 1 month prior to C1D1 and abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intraabdominal abscess and intestinal obstruction and/or clinical signs or symptoms of GI obstruction and intra-abdominal inflammatory process within 6 months prior to C1D1.
- Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to C1D1
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to C1D1; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to C1D1 Selicrelumab (Seli)– containing arm (Stage 1)
- Soluble CD25 > 2 x ULN
- Serum ferritin > 1000 ng/mL
- Known hereditary or acquired coagulopathy
- Concomitant treatment with anticoagulants Chemo – containing arm (Stage 2)
- Inability to tolerate atezo during Stage 1 and Patients with congenital long QT syndrome
Exclusion Criteria for the Nab-Paclitaxel-Containing Arms (Stage 1)
- Grade >= 2 neuropathy related to taxanes
Exclusion Criteria for the Tocilizumab-Containing Arm (Stage 1)
- Preexisting CNS demyelinating or seizure disorders
- History of diverticulitis, chronic ulcerative lower GI disease, or other symptomatic lower GI conditions that might predispose a patient to GI perforation
- Current liver disease unrelated to the underlying cancer diagnosis
- Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection, including, but not limited to, TB, atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail bed
- Active TB as documented by a positive purified protein derivative (PPD) skin test or TB blood test and confirmed by a positive chest X-ray within 3 months prior to initiation of study treatment
- Untreated latent TB
- History of, or currently active, primary or secondary immunodeficiency
- ALT or AST > 1.5 xULN or, for patients with liver metastases, > 3 x ULN
- Total bilirubin > ULN
Exclusion Criteria for the Sacituzumab Govitecan- Containing Arm (Stage 1)
- Prior treatment with a topoisomerase 1 inhibitor

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Männlich, Weiblich

Indikation
Brustkrebs

Medizinischer Befund
Triple-negative breast cancer (TNBC)

MedDRA Term
Triple negative breast cancer

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Martin Schuler

martin.schuler@uk-essen.de

Hufelandstraße 55
45147 Essen

Indikation
Lungenkrebs

Medizinischer Befund
PREVIOUSLY UNTREATED, KRAS G12C-MUTATED, ADVANCED OR-METASTATIC NON-SQUAMOUS NON-SMALL CELL LUNG CANCER 

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Prof. Dr. med. Jens Siveke

jens.siveke@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Roche Pharma AG, Grenzach-Wyhlen

Einschlusskriterien
- Histologically confirmed diagnosis of PDAC
- Pancreatic cancer tumor, lymph node, metastasis (TNM) pathological staging values of T1-T3, N0-N2, and M0 per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual
- Macroscopically complete (R0 or R1) resection of PDAC
- Unequivocal absence of disease after surgery as assessed by the investigator within 28 days prior to randomization
- CA19-9 level measured within 14 days prior to initiation of study treatment
- Interval of between 6 and 12 weeks since resection of PDAC
- Full recovery from surgery and ability to receive atezolizumab, autogene cevumeran, and mFOLFIRINOX in the investigator's judgment
- Adequate hematologic and end-organ function
- Female participants of childbearing potential must be willing to avoid pregnancy during the treatment period and for 28 days after the final dose of autogene cevumeran, for 9 months after the last dose of chemotherapy, and for 5 months after the final dose of atezolizumab.
- Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use specified contraceptive methods during the treatment period and for 28 days after the final dose of autogene cevumeran and for 6 months after the last dose of chemotherapy. Men must refrain from donating sperm during this same period.

Ausschlusskriterien
- Prior adjuvant, neoadjuvant, or induction treatment for pancreatic cancer
- Plan for further adjuvant anti-cancer therapy for PDAC (e.g., radiotherapy and/or chemotherapy), not mandated per protocol, to be initiated after completion of mFOLFIRINOX treatment
- Absence of spleen; distal pancreatectomy with splenectomy is exclusionary
- Preexisting Grade >/=2 neuropathy
- Known complete dihydropyrimidine dehydrogenase (DPD) deficiency including homozygous or compound heterozygous mutations of DPYD genetic locus associated with DPD deficiency
- Disorders of the colon or rectum, or postoperative complication leading to Grade >/=2 diarrhea
- Pregnancy or breastfeeding
- Active or history of autoimmune disease or immune deficiency
- Treatment with brivudine, sorivudine, or their chemically-related analogues, which are inhibitors of DPD, within 4 weeks prior to initiation of study treatment
- Current or planned treatment with strong inhibitors or inducers of CYP3A4 and/or UGT1A1.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Tumoren der Leber und Bauchspeicheldrüse und der Gallenwege

Medizinischer Befund
resected pancreatic ductal adenocarcinoma

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Bayer AG

Einschlusskriterien
- Participant must be ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consent.
- Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC).
- Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited.
- No prior systemic therapy for locally advanced or metastatic disease. No prior treatment with a HER2 ex20ins-targeted therapy (e.g. poziotinib, trastuzumab deruxtecan). Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening.
- Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information.

Ausschlusskriterien
- Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:
a. in situ cancers of cervix, breast, or skin,
b. superficial bladder cancer (Ta, Tis and T1),
c. limited-stage prostate cancer,
d. basal or squamous cancers of the skin.
- Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.
- Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for >4 weeks prior to planned start of study intervention.
- Pre-existing peripheral neuropathy that is Grade =2 by CTCAE (v5.0).
- History of severe hypersensitivity reaction to treatment with a monoclonal antibody.
- Prior radiotherapy outside of the brain within 21 days of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Advanced Non-small Cell Lung Cancer (NSCLC)\nHER2 Mutation

MedDRA Term
Non-small cell lung cancer, EGFR gene mutation

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Marcel Wiesweg

marcel.wiesweg@uk-essen.de

Hufelandstraße 55
45147 Essen

Sponsor

Astra Zeneca AB, Schweden

Einschlusskriterien
- Histologically or cytologically confirmed non-squamous NSCLC.
- Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKis] sensitivity [Ex19del, L858R, G719X, S768I, or L861Q], either alone or in combination with other EGFR mutations, which may include T790M).
- Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
- Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
- At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow reserve and organ function within 7 days before randomization.

Ausschlusskriterien
- Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
- Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
- Has significant third-space fluid retention (example [eg.], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
- History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
- Unstable spinal cord compression and/or unstable brain metastases.
- Participants with symptomatic brain metastases (including leptomeningeal involvement).
- Clinically significant corneal disease.
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
- Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Studienteilnehmende Mindestalter
18 Jahr(e)

Geschlecht
Divers, Männlich, Weiblich

Indikation
Lungenkrebs

Medizinischer Befund
Metastatic Non-small Cell Lung Cancer (NSCLC)

Institute
Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

Dr. med. Halime Kalkavan

halime.kalkavan@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

European Organisation for Research and Treatment of Cancer (EORTC), Belgien

Einschlusskriterien
- Primary non-metastatic UM, except iris melanoma, after definitive treatment either by surgery or radiotherapy
- Time from primary treatment smaller than 11 weeks (note that the maximum time between primary treatment and randomization is 12 weeks )
- High-risk according to either 1) clinical criteria: TNM (AJCC8) stage III or 2) genetic criteria: monosomy 3 or GEP class 2. Prior to enrolment of the first patient, each site will declare which of the two genetic criteria it uses. Patients with stage I and stage II are only eligible if they meet the genetic criterion declared by the site.
- ECOG performance status of 0 or 1
- 18 years or older
- HLA-A*02:01 positivity by local assessment
- No evidence of UM recurrence, as evidenced by the required baseline imaging performed within 4 weeks prior to randomization
- Adequate organ function
- Time-interval between the end of primary treatment and the randomization less than or equal to 12 weeks
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for women of childbearing potential (WOCBP) within 3 days prior to randomization.
- For patients of childbearing / reproductive potential, agreement to use adequate birth control measures during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
- For female subjects who are breast feeding, agreement to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
- Written informed consent according to ICH/GCP and local regulations

Ausschlusskriterien
- Clinically significant cardiac disease or impaired cardiac function, including any of the following:
- Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade = 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment
- QTcF > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome based on at least 3 ECGs obtained over a brief time interval (i.e., within 30 minutes)
- Acute myocardial infarction or unstable angina pectoris < 6 months prior to screening
- Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to randomization
- Any evidence of severe or uncontrolled systemic disease or active infection including hepatitis B, hepatitis C and known active human immunodeficiency virus (HIV) defined as >200 copies of HIV per ml of blood, active bleeding diatheses or renal transplant. NOTE: testing for HIV, HBV, and HCV status prior to enrolment is not necessary unless clinically indicated.
- Participant with history of HBV infection will be eligible if on stable anti-viral therapy for > 4 weeks prior to the planned first dose of study intervention and viral load confirmed as undetectable during Screening.
- Participant with history of HBC infection will be eligible the participant has received curative treatment and viral load was confirmed as undetectable during Screening.
- History of another primary malignancy except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and with the following exception. Patients with a history of another primary cancer treated with curative intent more than 3 years before study entry, who are not receiving any anti-cancer therapy, have a risk of disease recurrence lower than 10% as evaluated by the local Investigator, and who have no toxicity from previous treatment are eligible.
- Participants with active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn's disease), within 2 years of screening. NOTE: The following exceptions are permitted:
- Vitiligo
- Alopecia
- Managed hypothyroidism (on stable replacement doses)
- Asymptomatic adrenal insufficiency (on stable replacement doses)
- Psoriasis
- Resolved childhood asthma/atopy
- Well-controlled asthma
- Type I diabetes mellitus
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial.
- Known contraindication to imaging tracer or any product of contrast media and MRI and/or CT contraindications

Studienteilnehmende Mindestalter
18 Jahr(e)

Indikation
Melanom

Medizinischer Befund
Uveal melanoma

MedDRA Term
Uveal melanoma