Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)

NCT06469944 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 3475-06CMK-3475-06CKEYMAKER-06C2023-509307-33-00U1111-1299-8084
• Study Type: interventional
• Target: 160
• Locations: 12 countries
• Sites: 51

Brief Summary

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

Conditions

Gastroesophageal Junction; Gastroesophageal Adenocarcinoma; Esophageal Neoplasms; Esophageal Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (4)

• Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)

  DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be reported.

  Up to approximately 28 days

• Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to approximately 28 days

• Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  Up to approximately 28 days

• Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

  ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.

  Up to approximately 28 months

Secondary Outcomes (6)

• Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR

  Up to approximately 55 months

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

  Up to approximately 55 months

• Overall Survival (OS)

  Up to approximately 55 months

• Number of Participants Who Experience an Adverse Event (AE)

  Up to approximately 55 months

• Number of Participants Who Discontinue Study Treatment Due to an AE

  Up to approximately 55 months

Study Arms (3)

Pembrolizumab plus Chemotherapy

ACTIVE COMPARATOR

Participants will receive pembrolizumab 400 mg via intravenous (IV) injection on day 1 of every 6 week cycle (Q6W) for up to 18 cycles (up to \~2 years) AND investigator's choice of CAPOX chemotherapy (capecitabine 1000 mg/m\^2 orally twice daily for 14 days every 3 weeks (Q3W) and oxaliplatin 130 mg/m\^2 via IV infusion Q3W) OR mFOLFOX6 chemotherapy (oxaliplatin 85 mg/m\^2 via IV infusion Q3W; 5-Fluorouracil (5-FU) 400 mg/\^2 via bolus IV plus 2400 mg/m\^2 continuous IV once every 2 weeks (Q2W); and leucovorin 400 mg/m\^2 via IV infusion Q2W OR levoleucovorin 200 mg/m\^2 Q2W).

Biological: Pembrolizumab; Drug: Capecitabine; Drug: Leucovorin; Drug: Levoleucovorin; Drug: 5-Fluorouracil (5-FU); Drug: Oxaliplatin

Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

EXPERIMENTAL

Participants will receive sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to \~2 years) AND investigator's choice of capecitabine 1000 mg/m\^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/\^2 via bolus IV plus 2400 mg/m\^2 continuous IV once Q2W AND leucovorin 400 mg/m\^2 via IV infusion Q2W OR levoleucovorin 200 mg/m\^2 Q2W.

Biological: Pembrolizumab; Biological: Sacituzumab Tirumotecan (sac-TMT); Drug: Capecitabine; Drug: Leucovorin; Drug: Levoleucovorin; Drug: 5-Fluorouracil (5-FU)

Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy

EXPERIMENTAL

Participants will receive patritumab deruxtecan via IV infusion on Days 1 and 22 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to \~2 years) AND investigator's choice of capecitabine 1000 mg/m\^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/\^2 via bolus IV plus 2400 mg/m\^2 continuous IV once Q2W AND leucovorin 400 mg/m\^2 via IV infusion Q2W OR levoleucovorin 200 mg/m\^2 Q2W.

Biological: Pembrolizumab; Drug: Capecitabine; Drug: Leucovorin; Drug: Levoleucovorin; Drug: 5-Fluorouracil (5-FU); Biological: Patritumab Deruxtecan

Interventions

Pembrolizumab BIOLOGICAL

Administered via intravenous (IV) infusion.

Also known as: MK-3475, Keytruda®

Pembrolizumab plus Chemotherapy; Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy; Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Sacituzumab Tirumotecan (sac-TMT) BIOLOGICAL

Administered via IV infusion.

Also known as: MK-2870, SKB264

Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Capecitabine DRUG

Administered via oral tablet.

Also known as: XELODA

Pembrolizumab plus Chemotherapy; Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy; Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Leucovorin DRUG

Administered via IV infusion.

Also known as: calcium folinate, folinic acid, WELLCOVORIN®

Pembrolizumab plus Chemotherapy; Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy; Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Levoleucovorin DRUG

Administered via IV infusion.

Also known as: calcium levofolinate, levofolinic acid, FUSILEV®

Pembrolizumab plus Chemotherapy; Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy; Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

5-Fluorouracil (5-FU) DRUG

Administered via IV infusion

Also known as: ADRUCIL®

Pembrolizumab plus Chemotherapy; Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy; Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy

Oxaliplatin DRUG

Administered via IV infusion

Pembrolizumab plus Chemotherapy

Patritumab Deruxtecan BIOLOGICAL

Administered via IV infusion

Also known as: HER3-DXd, MK-1022, U3-1402

Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line (1L) gastroesophageal adenocarcinoma
• Is not expected to require tumor resection during the treatment course
• Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
• Core/excisional biopsy of a tumor lesion not previously irradiated has been provided
• Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
• Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible
• Has adequate organ function
• Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blinded independent central review (BICR)
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the first dose of study intervention
• Has a life expectancy of at least 6 months
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation/randomization
• Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy

You may not qualify if:

• Has squamous cell or undifferentiated gastroesophageal cancer.
• Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma
• Has experienced weight loss \>20% over 3 months before the first dose of study intervention
• Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
• Has Grade ≥2 peripheral neuropathy
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
• Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
• Has history of human immunodeficiency virus (HIV) infection with Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor receptor 3 (HER3) targeted agents
• Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC) and/or a topoisomerase I inhibitor-based chemotherapy
• Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
• Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)
• Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (51)

University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927)

Tucson, Arizona, 85719, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 6905)

Los Angeles, California, 90404, United States

RECRUITING

Norton Hospital-Norton Cancer Institute - Downtown ( Site 6900)

Louisville, Kentucky, 40202, United States

COMPLETED

The Cancer and Hematology Centers ( Site 6912)

Grand Rapids, Michigan, 49503, United States

RECRUITING

Hematology-Oncology Associates of Central NY, P.C. ( Site 6925)

East Syracuse, New York, 13057, United States

RECRUITING

Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 6907)

New York, New York, 10032, United States

COMPLETED

UPMC Hillman Cancer Center-UPMC ( Site 6904)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Texas MD Anderson Cancer Center ( Site 6920)

Houston, Texas, 77030, United States

RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 6303)

Natal, Rio Grande do Norte, 59062-000, Brazil

RECRUITING

Hospital Nossa Senhora da Conceição ( Site 6301)

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

RECRUITING

ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300)

São Paulo, 01246-000, Brazil

RECRUITING

IBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304)

São Paulo, 03102-006, Brazil

RECRUITING

Clínica Puerto Montt ( Site 6409)

Port Montt, Los Lagos Region, 5500243, Chile

RECRUITING

Centro de Investigación del Maule ( Site 6408)

Talca, Maule Region, 3481349, Chile

RECRUITING

FALP-UIDO ( Site 6400)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Oncología de Precisión-Oncology ( Site 6404)

Santiago, Region M. de Santiago, 7560908, Chile

RECRUITING

Clínica UC San Carlos de Apoquindo ( Site 6405)

Santiago, Region M. de Santiago, 7620002, Chile

RECRUITING

Bradfordhill-Clinical Area ( Site 6401)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Bradford Hill Norte ( Site 6407)

Antofagasta, 1263521, Chile

RECRUITING

Beijing Cancer hospital-Digestive Oncology ( Site 5500)

Beijing, Beijing Municipality, 100142, China

RECRUITING

The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501)

Fuzhou, Fujian, 350025, China

RECRUITING

The First Affiliated hospital of Xiamen University ( Site 5503)

Xiamen, Fujian, 361003, China

RECRUITING

Henan Cancer Hospital ( Site 5504)

Zhengzhou, Henan, 450008, China

RECRUITING

The First Affiliated Hospital of Nanchang University ( Site 5514)

Nanchang, Jiangxi, 330000, China

RECRUITING

Fudan University Shanghai Cancer Center ( Site 5513)

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Xinjiang Medical University Cancer Hospital - Urumqi ( Site 5506)

Ürümqi, Xinjiang, 841100, China

RECRUITING

Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 5510)

Hangzhou, Zhejiang, 310016, China

RECRUITING

CHU-BREST Cavale Blanche ( Site 5104)

Brest, Finistere, 29200, France

RECRUITING

CIC. ( Site 5100)

Lille, Nord, 59037, France

RECRUITING

Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 5102)

Paris, Île-de-France Region, 75013, France

RECRUITING

NCT-Department of Medical Oncology ( Site 6809)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802)

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 6806)

Dresden, Saxony, 01307, Germany

RECRUITING

Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 6807)

Hamburg, 20249, Germany

RECRUITING

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 5207)

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 5200)

Milan, Lombardy, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana ( Site 5206)

Pisa, Tuscany, 56126, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 5202)

Milan, 20132, Italy

RECRUITING

Oslo universitetssykehus, Radiumhospitalet ( Site 6501)

Oslo, 0379, Norway

RECRUITING

Asan Medical Center-Department of Oncology ( Site 5901)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 5900)

Seoul, 06351, South Korea

RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 6701)

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Kantonsspital Graubünden-Medizin ( Site 6700)

Chur, Kanton Graubünden, 7000, Switzerland

RECRUITING

China Medical University Hospital ( Site 6007)

Taichung, 404, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 6001)

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital-Oncology ( Site 6000)

Taipei, 10048, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 6005)

Taipei, 112, Taiwan

RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 6102)

Bangkoknoi, Bangkok, 10700, Thailand

RECRUITING

Chulalongkorn Hospital ( Site 6104)

Pathumwan, Bangkok, 10330, Thailand

RECRUITING

Ramathibodi Hospital ( Site 6103)

Ratchathewi, Bangkok, 10400, Thailand

RECRUITING

Songklanagarind hospital ( Site 6101)

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Capecitabine; Leucovorin; Levoleucovorin; Fluorouracil; Oxaliplatin; patritumab deruxtecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 24, 2024
• Study Start: September 20, 2024
• Primary Completion (Estimated): September 12, 2029
• Study Completion (Estimated): September 12, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CH (2); FR (3); IT (4); US (8); NO (1); CN (8); CL (7); TW (4); BR (4); DE (4); TH (4); KR (2)