Actively Recruiting
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)
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-01
160
Participants Needed
50
Research Sites
259 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official 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...
- Histologically or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line gastroesophageal adenocarcinoma
- Tumor tissue negative for HER2 expression according to ASCO-CAP guidelines
- Provided core or excisional biopsy of a tumor lesion not previously irradiated
- Recovered to Grade 1 or baseline from previous anticancer therapy adverse events
- Endocrine-related adverse events adequately treated with hormone replacement therapy
- Adequate organ function
- Measurable disease per RECIST 1.1 as confirmed by independent central review
- ECOG performance status of 0 or 1 within 3 days prior to first dose
- Life expectancy of at least 6 months
- Hepatitis B surface antigen positive participants must have received antiviral therapy for at least 4 weeks with undetectable viral load
- Participants with history of hepatitis C virus infection must have undetectable viral load at screening
- HIV-infected participants must have well-controlled HIV on antiretroviral therapy
You will not qualify if you...
- Diagnosis of 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 dose
- History of severe dry eye syndrome, severe Meibomian gland disease, blepharitis, or severe corneal disease preventing or delaying healing
- Grade 2 or higher peripheral neuropathy
- Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- Uncontrolled significant cardiovascular or cerebrovascular disease within 6 months preceding study
- Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretics within 2 weeks prior to enrollment
- History of HIV infection with Kaposi's sarcoma or Multicentric Castleman's Disease
- Prior treatment with TROP2-targeted or anti-HER3 agents
- Prior treatment with topoisomerase I inhibitor-based ADC or chemotherapy
- Prior systemic anticancer therapy within 4 weeks before first dose
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2 agents or other T-cell receptor-directed agents
- Prior radiotherapy within 2 weeks of study start or radiation-related toxicities requiring corticosteroids
- Receipt of live or live-attenuated vaccine within 30 days before first dose
- Use of strong CYP3A4 inducer or inhibitor that cannot be discontinued
- Use of investigational agent or device within 4 weeks prior to study intervention
- Diagnosis of immunodeficiency or receiving chronic systemic steroid or other immunosuppressive therapy within 7 days before first dose
- Known additional malignancy progressing or requiring active treatment within past 3 years
- Active CNS metastases or carcinomatous meningitis
- Severe hypersensitivity (Grade 3 or higher) to study drugs or their excipients
- Active autoimmune disease requiring systemic treatment in past 2 years
- History or current pneumonitis or interstitial lung disease requiring steroids or suspected but unruled out
- Active infection requiring systemic therapy
- Concurrent active hepatitis B and hepatitis C infections
- Conditions or therapies that might interfere with study results or participant cooperation
- Gastrointestinal obstruction, poor oral intake, or difficulty taking oral medication
- Poorly controlled diarrhea
- Major surgery or significant 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
Trial Site Locations
Total: 50 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
Songklanagarind hospital ( Site 6101)
Hat Yai, Changwat Songkhla, Thailand, 90110
Actively Recruiting
Research Team
T
Toll Free Number
CONTACT
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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