Actively Recruiting
A Phase 1/2 Open-Label Study of Investigational Agents With Pembrolizumab and Chemotherapy for First-Line Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma (Substudy 06C)
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-26
160
Participants Needed
51
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and tolerability of investigational agents combined with pembrolizumab and fluoropyrimidine chemotherapy for first-line treatment of participants with locally advanced unresectable or metastatic HER2-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This phase 1/2, multicenter, open-label umbrella platform study includes a safety lead-in phase to assess dose-limiting toxicities and adverse events and an efficacy phase to establish recommended dosing and evaluate treatment effects. Participants will be randomly assigned to one of three groups: pembrolizumab plus chemotherapy, pembrolizumab plus sacituzumab tirumotecan plus chemotherapy, or pembrolizumab plus patritumab deruxtecan plus chemotherapy. Pembrolizumab is given via intravenous infusion every 6 weeks for up to 18 cycles (about 2 years). Chemotherapy options include CAPOX or mFOLFOX6 regimens, administered in cycles every 2 to 3 weeks. Sacituzumab tirumotecan and patritumab deruxtecan are also given by intravenous infusion on specific days in 6-week cycles until discontinuation. Throughout the study, participants will undergo monitoring for safety and treatment effects, including assessments of dose-limiting toxicities, adverse events, and objective tumor response by independent review. Other outcomes measured include progression-free survival, duration of response, overall survival, and immune response to investigational agents. The study may last up to approximately 55 months, with ongoing safety evaluations and data collection to understand the impact of these treatments on advanced gastroesophageal adenocarcinoma.
CONDITIONS
Brief Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histologically or cytologically confirmed untreated locally advanced unresectable or metastatic first-line gastroesophageal adenocarcinoma
- Tumor tissue confirmed HER2-negative according to ASCO-CAP guidelines
- Core or excisional biopsy of a tumor lesion not previously irradiated provided
- Recovery to Grade 1 or baseline from adverse events of prior anticancer therapies
- Adequately treated endocrine-related adverse events with hormone replacement therapy
- Adequate organ function
- Measurable disease per RECIST 1.1 verified by independent review
- ECOG performance status of 0 or 1 within 3 days before first study dose
- Life expectancy of at least 6 months
- Hepatitis B participants must have received antiviral therapy for at least 4 weeks with undetectable viral load
- Hepatitis C participants must have undetectable viral load at screening
- Well-controlled HIV infection on antiretroviral therapy
You will not qualify if you...
- Squamous cell or undifferentiated gastroesophageal cancer
- Previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction/esophageal adenocarcinoma
- Weight loss greater than 20% over 3 months before first study dose
- Severe dry eye syndrome, severe Meibomian gland disease, blepharitis, or severe corneal disease delaying healing
- Grade 2 or higher peripheral neuropathy
- Active or history of inflammatory bowel disease requiring immunosuppressive medication
- Uncontrolled significant cardiovascular or cerebrovascular disease within 6 months prior to study
- Pleural, ascitic, or pericardial fluid accumulation requiring drainage or diuretics within 2 weeks prior to enrollment
- HIV infection with Kaposi's sarcoma or Multicentric Castleman's Disease
- Prior treatment with TROP2-targeted or HER3-targeted agents
- Prior treatment with topoisomerase I inhibitor-based antibody-drug conjugate or chemotherapy
- Systemic anticancer therapy within 4 weeks before first study dose
- Anti-PD-1, PD-L1, PD-L2, or other T-cell receptor agent therapy prior to study
- Radiotherapy within 2 weeks before study start or radiation-related toxicities requiring corticosteroids
- Live or live-attenuated vaccine within 30 days before first dose
- Use of strong CYP3A4 inducers or inhibitors that cannot be stopped
- Investigational agent or device use within 4 weeks before study
- Immunodeficiency or chronic systemic steroid or immunosuppressive therapy within 7 days before first dose
- Progressing additional malignancy requiring active treatment in past 3 years
- Active central nervous system metastases or carcinomatous meningitis
- Severe hypersensitivity to study drugs or excipients
- Active autoimmune disease requiring systemic treatment in past 2 years
- Pneumonitis or interstitial lung disease requiring steroids or suspected cases not ruled out
- Active infection requiring systemic therapy
- Concurrent active hepatitis B and hepatitis C infection
- Conditions or therapies interfering with study results or cooperation
- Gastrointestinal obstruction or difficulty taking oral medications
- Poorly controlled diarrhea
- Major surgery or significant traumatic injury within 4 weeks before first dose
- History of allogeneic tissue or solid organ transplant
- Incomplete recovery from major surgery or ongoing surgical complications
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 2 years
Participants receive pembrolizumab and chemotherapy with or without investigational agents for up to approximately 2 years, involving intravenous infusions and oral medications according to their assigned treatment arm.
Repeated visits every 6 weeks for pembrolizumab infusion and chemotherapy cycles administered every 2 to 3 weeks depending on regimen
Duration - Up to approximately 3 years
Participants are monitored for safety, disease response, and survival outcomes after treatment completion.
Periodic visits as scheduled for assessments up to approximately 55 months
Trial Site Locations
Total: 51 locations
1
University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927)
Tucson, Arizona, United States, 85719
Actively Recruiting
2
UCLA Hematology/Oncology - Santa Monica ( Site 6905)
Los Angeles, California, United States, 90404
Actively Recruiting
3
Norton Hospital-Norton Cancer Institute - Downtown ( Site 6900)
Louisville, Kentucky, United States, 40202
Completed
4
The Cancer and Hematology Centers ( Site 6912)
Grand Rapids, Michigan, United States, 49503
Actively Recruiting
5
Hematology-Oncology Associates of Central NY, P.C. ( Site 6925)
East Syracuse, New York, United States, 13057
Actively Recruiting
6
Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 6907)
New York, New York, United States, 10032
Completed
7
UPMC Hillman Cancer Center-UPMC ( Site 6904)
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
8
University of Texas MD Anderson Cancer Center ( Site 6920)
Houston, Texas, United States, 77030
Actively Recruiting
9
Liga Norte Riograndense Contra o Câncer ( Site 6303)
Natal, Rio Grande do Norte, Brazil, 59062-000
Actively Recruiting
10
Hospital Nossa Senhora da Conceição ( Site 6301)
Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
Actively Recruiting
11
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300)
São Paulo, Brazil, 01246-000
Actively Recruiting
12
IBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304)
São Paulo, Brazil, 03102-006
Actively Recruiting
13
Clínica Puerto Montt ( Site 6409)
Port Montt, Los Lagos Region, Chile, 5500243
Actively Recruiting
14
Centro de Investigación del Maule ( Site 6408)
Talca, Maule Region, Chile, 3481349
Actively Recruiting
15
FALP-UIDO ( Site 6400)
Santiago, Region M. de Santiago, Chile, 7500921
Actively Recruiting
16
Centro de Oncología de Precisión-Oncology ( Site 6404)
Santiago, Region M. de Santiago, Chile, 7560908
Actively Recruiting
17
Clínica UC San Carlos de Apoquindo ( Site 6405)
Santiago, Region M. de Santiago, Chile, 7620002
Actively Recruiting
18
Bradfordhill-Clinical Area ( Site 6401)
Santiago, Region M. de Santiago, Chile, 8420383
Actively Recruiting
19
Bradford Hill Norte ( Site 6407)
Antofagasta, Chile, 1263521
Actively Recruiting
20
Beijing Cancer hospital-Digestive Oncology ( Site 5500)
Beijing, Beijing Municipality, China, 100142
Actively Recruiting
21
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501)
Fuzhou, Fujian, China, 350025
Actively Recruiting
22
The First Affiliated hospital of Xiamen University ( Site 5503)
Xiamen, Fujian, China, 361003
Actively Recruiting
23
Henan Cancer Hospital ( Site 5504)
Zhengzhou, Henan, China, 450008
Actively Recruiting
24
The First Affiliated Hospital of Nanchang University ( Site 5514)
Nanchang, Jiangxi, China, 330000
Actively Recruiting
25
Fudan University Shanghai Cancer Center ( Site 5513)
Shanghai, Shanghai Municipality, China, 200032
Actively Recruiting
26
Xinjiang Medical University Cancer Hospital - Urumqi ( Site 5506)
Ürümqi, Xinjiang, China, 841100
Actively Recruiting
27
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 5510)
Hangzhou, Zhejiang, China, 310016
Actively Recruiting
28
CHU-BREST Cavale Blanche ( Site 5104)
Brest, Finistere, France, 29200
Actively Recruiting
29
CIC. ( Site 5100)
Lille, Nord, France, 59037
Actively Recruiting
30
Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 5102)
Paris, Île-de-France Region, France, 75013
Actively Recruiting
31
NCT-Department of Medical Oncology ( Site 6809)
Heidelberg, Baden-Wurttemberg, Germany, 69120
Actively Recruiting
32
Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802)
Düsseldorf, North Rhine-Westphalia, Germany, 40225
Actively Recruiting
33
Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 6806)
Dresden, Saxony, Germany, 01307
Actively Recruiting
34
Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 6807)
Hamburg, Germany, 20249
Actively Recruiting
35
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 5207)
Meldola, Emilia-Romagna, Italy, 47014
Actively Recruiting
36
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 5200)
Milan, Lombardy, Italy, 20133
Actively Recruiting
37
Azienda Ospedaliero Universitaria Pisana ( Site 5206)
Pisa, Tuscany, Italy, 56126
Actively Recruiting
38
Ospedale San Raffaele-Oncologia Medica ( Site 5202)
Milan, Italy, 20132
Actively Recruiting
39
Oslo universitetssykehus, Radiumhospitalet ( Site 6501)
Oslo, Norway, 0379
Actively Recruiting
40
Asan Medical Center-Department of Oncology ( Site 5901)
Seoul, South Korea, 05505
Actively Recruiting
41
Samsung Medical Center-Division of Hematology/Oncology ( Site 5900)
Seoul, South Korea, 06351
Actively Recruiting
42
Hôpitaux Universitaires de Genève (HUG) ( Site 6701)
Geneva, Canton of Geneva, Switzerland, 1211
Actively Recruiting
43
Kantonsspital Graubünden-Medizin ( Site 6700)
Chur, Kanton Graubünden, Switzerland, 7000
Actively Recruiting
44
China Medical University Hospital ( Site 6007)
Taichung, Taiwan, 404
Actively Recruiting
45
National Cheng Kung University Hospital ( Site 6001)
Tainan, Taiwan, 704
Actively Recruiting
46
National Taiwan University Hospital-Oncology ( Site 6000)
Taipei, Taiwan, 10048
Actively Recruiting
47
Taipei Veterans General Hospital ( Site 6005)
Taipei, Taiwan, 112
Actively Recruiting
48
Faculty of Medicine Siriraj Hospital ( Site 6102)
Bangkoknoi, Bangkok, Thailand, 10700
Actively Recruiting
49
Chulalongkorn Hospital ( Site 6104)
Pathumwan, Bangkok, Thailand, 10330
Actively Recruiting
50
Ramathibodi Hospital ( Site 6103)
Ratchathewi, Bangkok, Thailand, 10400
Actively Recruiting
51
Songklanagarind hospital ( Site 6101)
Hat Yai, Changwat Songkhla, Thailand, 90110
Actively Recruiting
Research Team
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How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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