Substudy 06C: A Study of Sacituzumab Tirumotecan (MK-2870) 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: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
130 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 sacituzumab tirumotecan in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy
Participants will receive sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 6 week cycle until discontinuation, pembrolizumab 400 mg via IV injection on day 1 of every 6 week cycle 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.
Pembrolizumab
Administered via intravenous (IV) infusion.
Sacituzumab Tirumotecan (sac-TMT)
Administered via IV infusion.
Capecitabine
Administered via oral tablet.
5-FU
Administered via IV infusion
Pembrolizumab plus Chemotherapy
Participants will receive pembrolizumab 400 mg via intravenous (IV) injection on day 1 of every 6 week cycle 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-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-FU
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-FU
Administered via IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu-positive are excluded. HER2 status is not required if HER2/neu testing is not mandatory per local standard of care (SOC)
* Is not expected to require tumor resection during the treatment course
* Has not had prior systemic therapy administered in the recurrent or metastatic setting
* Has provided an archival tumor tissue sample or most recently obtained core, or incisional, or excisional biopsy for a tumor lesion
* 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 blind independent review committee (BICR)
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 3 days before allocation/randomization.
* Has a life expectancy of at least 6 months
* 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 randomization.
* Who has 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 (ART)
Exclusion Criteria
* Has had previous therapy for locally advanced unresectable or metastatic gastric/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
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC)
* Has received prior treatment with a topoisomerase I inhibitor-based ADC and/or a topoisomerase I inhibitor-based chemotherapy
* Has received prior systemic anticancer therapy including investigational agents 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, 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/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* 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
* Has 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
* Have not adequately recovered from major surgery or have 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