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RECRUITING Phase 1 / Phase 2 ClinicalTrials.gov

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)

Sponsor: Merck Sharp & Dohme LLC • ClinicalTrials.gov ID: NCT06469944

Registry updated: 2026-10-07
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Description

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.

Interventions

  • Pembrolizumab (Biological)
    Administered via intravenous (IV) infusion.
  • Sacituzumab Tirumotecan (sac-TMT) (Biological)
    Administered via IV infusion.
  • Capecitabine (Drug)
    Administered via oral tablet.
  • Leucovorin (Drug)
    Administered via IV infusion.
  • Levoleucovorin (Drug)
    Administered via IV infusion.
  • 5-Fluorouracil (5-FU) (Drug)
    Administered via IV infusion
  • Oxaliplatin (Drug)
    Administered via IV infusion
  • Patritumab Deruxtecan (Biological)
    Administered via IV infusion

Eligibility criteria

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * 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 Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * 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 * Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, patritumab deruxtecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening * Has an active infection requiring systemic therapy * Has concurrent active hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-hepatitis C virus \[HCV\] Ab positive and detectable HCV ribonucleic acid \[RNA\] infection or a known history of hepatitis B and/or C infection * Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study * Has gastrointestinal (GI) obstruction, poor oral intake, or difficulty in taking oral medication * Has poorly controlled diarrhea * Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention * Has history of allogeneic tissue/solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications

Conditions

Gastroesophageal Junction Gastroesophageal Adenocarcinoma Esophageal Neoplasms Esophageal Cancer

Locations

  • University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927) — Tucson, Arizona, United States
  • UCLA Hematology/Oncology - Santa Monica ( Site 6905) — Los Angeles, California, United States
  • Norton Hospital-Norton Cancer Institute - Downtown ( Site 6900) — Louisville, Kentucky, United States
  • The Cancer and Hematology Centers ( Site 6912) — Grand Rapids, Michigan, United States
  • Hematology-Oncology Associates of Central NY, P.C. ( Site 6925) — East Syracuse, New York, United States
  • Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 6907) — New York, New York, United States
  • UPMC Hillman Cancer Center-UPMC ( Site 6904) — Pittsburgh, Pennsylvania, United States
  • University of Texas MD Anderson Cancer Center ( Site 6920) — Houston, Texas, United States
  • Liga Norte Riograndense Contra o Câncer ( Site 6303) — Natal, Rio Grande do Norte, Brazil
  • Hospital Nossa Senhora da Conceição ( Site 6301) — Porto Alegre, Rio Grande do Sul, Brazil
  • ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300) — São Paulo, Brazil
  • IBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304) — São Paulo, Brazil
  • Clínica Puerto Montt ( Site 6409) — Port Montt, Los Lagos Region, Chile
  • Centro de Investigación del Maule ( Site 6408) — Talca, Maule Region, Chile
  • FALP-UIDO ( Site 6400) — Santiago, Region M. de Santiago, Chile
  • Centro de Oncología de Precisión-Oncology ( Site 6404) — Santiago, Region M. de Santiago, Chile
  • Clínica UC San Carlos de Apoquindo ( Site 6405) — Santiago, Region M. de Santiago, Chile
  • Bradfordhill-Clinical Area ( Site 6401) — Santiago, Region M. de Santiago, Chile
  • Bradford Hill Norte ( Site 6407) — Antofagasta, Chile
  • Beijing Cancer hospital-Digestive Oncology ( Site 5500) — Beijing, Beijing Municipality, China
  • The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501) — Fuzhou, Fujian, China
  • The First Affiliated hospital of Xiamen University ( Site 5503) — Xiamen, Fujian, China
  • Henan Cancer Hospital ( Site 5504) — Zhengzhou, Henan, China
  • The First Affiliated Hospital of Nanchang University ( Site 5514) — Nanchang, Jiangxi, China
  • Fudan University Shanghai Cancer Center ( Site 5513) — Shanghai, Shanghai Municipality, China
  • Xinjiang Medical University Cancer Hospital - Urumqi ( Site 5506) — Ürümqi, Xinjiang, China
  • Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 5510) — Hangzhou, Zhejiang, China
  • CHU-BREST Cavale Blanche ( Site 5104) — Brest, Finistere, France
  • CIC. ( Site 5100) — Lille, Nord, France
  • Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 5102) — Paris, Île-de-France Region, France
  • NCT-Department of Medical Oncology ( Site 6809) — Heidelberg, Baden-Wurttemberg, Germany
  • HOPE Hamburg/Norddeutsches Studienzentrum fuer Innovative Onkologie ( Site 6807) — Erdgeschoss, Free and Hanseatic City of Hamburg, Germany
  • Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802) — Düsseldorf, North Rhine-Westphalia, Germany
  • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 5207) — Meldola, Emilia-Romagna, Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 5200) — Milan, Lombardy, Italy
  • Azienda Ospedaliero Universitaria Pisana ( Site 5206) — Pisa, Tuscany, Italy
  • Ospedale San Raffaele-Oncologia Medica ( Site 5202) — Milan, Italy
  • Oslo universitetssykehus, Radiumhospitalet ( Site 6501) — Oslo, Norway
  • Asan Medical Center-Department of Oncology ( Site 5901) — Seoul, South Korea
  • Samsung Medical Center-Division of Hematology/Oncology ( Site 5900) — Seoul, South Korea
  • Hôpitaux Universitaires de Genève (HUG) ( Site 6701) — Geneva, Canton of Geneva, Switzerland
  • Kantonsspital Graubünden-Medizin ( Site 6700) — Chur, Kanton Graubünden, Switzerland
  • China Medical University Hospital ( Site 6007) — Taichung, Taiwan
  • National Cheng Kung University Hospital ( Site 6001) — Tainan, Taiwan
  • National Taiwan University Hospital-Oncology ( Site 6000) — Taipei, Taiwan
  • Taipei Veterans General Hospital ( Site 6005) — Taipei, Taiwan
  • Faculty of Medicine Siriraj Hospital ( Site 6102) — Bangkoknoi, Bangkok, Thailand
  • Chulalongkorn Hospital ( Site 6104) — Pathumwan, Bangkok, Thailand
  • Ramathibodi Hospital ( Site 6103) — Ratchathewi, Bangkok, Thailand
  • Songklanagarind hospital ( Site 6101) — Hat Yai, Changwat Songkhla, Thailand
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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

View Official Record