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)
NCT ID: NCT06469944
Last Updated: 2026-01-05
Study Results
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Basic Information
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RECRUITING
PHASE1/PHASE2
160 participants
INTERVENTIONAL
2024-09-20
2029-04-12
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab plus Chemotherapy
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).
Pembrolizumab
Administered via intravenous (IV) infusion.
Capecitabine
Administered via oral tablet.
Leucovorin
Administered via IV infusion.
Levoleucovorin
Administered via IV infusion.
5-Fluorouracil (5-FU)
Administered via IV infusion
Oxaliplatin
Administered via IV infusion
Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy
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.
Pembrolizumab
Administered via intravenous (IV) infusion.
Sacituzumab Tirumotecan (sac-TMT)
Administered via IV infusion.
Capecitabine
Administered via oral tablet.
Leucovorin
Administered via IV infusion.
Levoleucovorin
Administered via IV infusion.
5-Fluorouracil (5-FU)
Administered via IV infusion
Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy
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.
Pembrolizumab
Administered via intravenous (IV) infusion.
Capecitabine
Administered via oral tablet.
Leucovorin
Administered via IV infusion.
Levoleucovorin
Administered via IV infusion.
5-Fluorouracil (5-FU)
Administered via IV infusion
Patritumab Deruxtecan
Administered via IV infusion
Interventions
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Pembrolizumab
Administered via intravenous (IV) infusion.
Sacituzumab Tirumotecan (sac-TMT)
Administered via IV infusion.
Capecitabine
Administered via oral tablet.
Leucovorin
Administered via IV infusion.
Levoleucovorin
Administered via IV infusion.
5-Fluorouracil (5-FU)
Administered via IV infusion
Oxaliplatin
Administered via IV infusion
Patritumab Deruxtecan
Administered via IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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 (noninfectious) pneumonitis or interstitial lung disease (ILD) that required steroids or has current pneumonitis or ILD, or where suspected ILD or pneumonitis 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
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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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
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
Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802)
Düsseldorf, North Rhine-Westphalia, Germany
Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 6807)
Hamburg, , 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
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
Countries
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Central Contacts
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Facility Contacts
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-06C
Identifier Type: OTHER
Identifier Source: secondary_id
KEYMAKER-06C
Identifier Type: OTHER
Identifier Source: secondary_id
2023-509307-33-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1299-8084
Identifier Type: REGISTRY
Identifier Source: secondary_id
3475-06C
Identifier Type: -
Identifier Source: org_study_id
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