Actively Recruiting
Phase 1/2 Study of Sacituzumab Tirumotecan, HER3-DXd, and Ramucirumab Combinations as Second-Line Treatment for Advanced Gastroesophageal Adenocarcinoma
Led by Merck Sharp & Dohme LLC · Updated on 2026-05-12
210
Participants Needed
45
Research Sites
117 weeks
Total Duration
On this page
Sponsors
M
Merck Sharp & Dohme LLC
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of new combination treatments for people with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma who have not responded to one prior treatment. This Phase 1/2 open-label study compares sacituzumab tirumotecan plus paclitaxel versus ramucirumab plus paclitaxel, and HER3-DXd plus ramucirumab versus ramucirumab plus paclitaxel. The study is designed as an estimation study without formal hypothesis testing and is part of the larger KEYMAKER-U06 master protocol. Participants will be randomly assigned to one of three treatment groups. One group receives ramucirumab by intravenous (IV) infusion every two weeks plus paclitaxel weekly for three weeks in a four-week cycle, continuing for about 60 weeks. Another group starts with a 28-day run-in of sacituzumab tirumotecan at two doses plus paclitaxel, followed by continued paclitaxel and sacituzumab tirumotecan infusions every six weeks until treatment ends. The third group receives HER3-DXd and ramucirumab by IV infusion on specific days in a six-week cycle until discontinuation. During the study, participants will have regular assessments for side effects, tumor response, and overall health, including monitoring for dose-limiting toxicities and adverse events. Researchers will measure objective response rates over about 28 months and track progression-free survival, response duration, and overall survival up to 50 months. Safety labs, biopsies, and imaging will be performed, and participants will be followed for long-term outcomes and immune responses to the study drugs. The total study duration varies with ongoing treatment and follow-up.
CONDITIONS
Brief Title
Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults 18 years or older
- Histologically or cytologically confirmed advanced or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
- Disease progressed during or after first-line therapy including platinum/fluoropyrimidine with or without immunotherapy
- Tumor confirmed HER2-negative by ASCO-CAP guidelines
- Ability to provide core or excisional biopsy of a tumor lesion not previously irradiated
- Adverse events from prior therapies must be grade 1 or baseline, except alopecia and vitiligo
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy of at least 3 months
- Hepatitis B surface antigen positive participants eligible if on antiviral therapy with undetectable viral load
- Hepatitis C participants eligible if viral load is undetectable
- Well-controlled HIV infection on antiretroviral therapy
You will not qualify if you...
- Squamous cell or undifferentiated gastroesophageal cancer
- Weight loss greater than 20% in 3 months before study
- Severe dry eye syndrome, Meibomian gland disease, blepharitis, or corneal disease delaying healing
- Grade 2 or higher peripheral neuropathy
- Active or history of inflammatory bowel disease requiring immunosuppressive treatment
- Serious or nonhealing wounds, peptic ulcers, or bone fractures within 28 days before study
- Bowel obstruction, inflammatory enteropathy, or extensive intestinal resection with chronic diarrhea
- Uncontrolled cardiovascular or cerebrovascular disease
- Arterial thrombotic event within 6 months before study
- Uncontrolled hypertension (≥150/90 mm Hg)
- Significant fluid accumulation requiring drainage or diuretics within 2 weeks before study
- Major surgery within 28 days or central venous access device placement within 7 days before study
- Therapeutic anticoagulation or chronic use of NSAIDs or antiplatelet agents
- History of deep vein thrombosis, pulmonary embolism, or other thromboembolism within 3 months
- Significant bleeding disorders or recent gastrointestinal bleeding within 3 months
- History of gastrointestinal perforation or fistula within 6 months
- HIV with Kaposi's sarcoma or Multicentric Castleman's Disease
- Prior treatment with TROP2- or HER3-targeted agents, topoisomerase 1 inhibitor ADCs or chemotherapy, or VEGF/VEGFR-targeted therapy
- Systemic anticancer therapy within 4 weeks before study
- Radiotherapy within 2 weeks before study or radiation-related toxicities requiring corticosteroids
- Live or live-attenuated vaccine within 30 days before study
- Investigational agent or device within 4 weeks before study
- Other active malignancies requiring treatment within 3 years, except certain skin and bladder carcinomas
- Active central nervous system metastases or carcinomatous meningitis
- Active infection requiring systemic therapy
- Concurrent active hepatitis B and C infection
- History or current pneumonitis/interstitial lung disease requiring steroids
- Severe hypersensitivity to study drugs or biologic therapies
- 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 - 28 days
Participants receive sacituzumab tirumotecan at 3 mg/kg and 4 mg/kg via IV infusion on Days 1 and 15 of a 6-week cycle plus paclitaxel at 80 mg/m² IV infusion on Days 1, 8, and 15 of a 4-week cycle.
Multiple visits during 4 weeks
Duration - Up to approximately 60 weeks
Participants receive assigned combination therapy: either ramucirumab plus paclitaxel, sacituzumab tirumotecan plus paclitaxel, or HER3-DXd plus ramucirumab, administered via IV infusion on scheduled days in cycles until discontinuation.
Regular IV infusion visits every 1 to 3 weeks depending on treatment arm
Duration - Up to approximately 50 months
Participants are monitored for safety and survival outcomes after treatment ends.
Periodic follow-up visits
Trial Site Locations
Total: 45 locations
1
University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927)
Tucson, Arizona, United States, 85719
Actively Recruiting
2
UCLA Hematology/Oncology - Santa Monica ( Site 8905)
Los Angeles, California, United States, 90404
Actively Recruiting
3
Norton Cancer Institute - Downtown ( Site 8900)
Louisville, Kentucky, United States, 40202
Completed
4
The Cancer and Hematology Centers ( Site 8912)
Grand Rapids, Michigan, United States, 49503
Actively Recruiting
5
Hematology-Oncology Associates of Central NY, P.C. ( Site 8925)
East Syracuse, New York, United States, 13057
Actively Recruiting
6
Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 8907)
New York, New York, United States, 10032
Completed
7
UPMC Hillman Cancer Center-UPMC ( Site 8904)
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
8
University of Texas MD Anderson Cancer Center ( Site 8920)
Houston, Texas, United States, 77030
Actively Recruiting
9
Liga Norte Riograndense Contra o Câncer ( Site 8303)
Natal, Rio Grande do Norte, Brazil, 59062-000
Actively Recruiting
10
Hospital Nossa Senhora da Conceição ( Site 8301)
Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
Actively Recruiting
11
IBCC - Instituto Brasileiro de Controle do Câncer ( Site 8304)
São Paulo, São Paulo, Brazil, 03102-002
Actively Recruiting
12
Clínica Puerto Montt ( Site 8409)
Port Montt, Los Lagos Region, Chile, 5500243
Actively Recruiting
13
Centro de Investigación del Maule ( Site 8408)
Talca, Maule Region, Chile, 3481349
Actively Recruiting
14
FALP-UIDO ( Site 8400)
Santiago, Region M. de Santiago, Chile, 7500921
Actively Recruiting
15
Centro de Oncología de Precisión-Oncology ( Site 8404)
Santiago, Region M. de Santiago, Chile, 7560908
Actively Recruiting
16
Clínica UC San Carlos de Apoquindo ( Site 8405)
Santiago, Region M. de Santiago, Chile, 7620002
Actively Recruiting
17
Bradfordhill-Clinical Area ( Site 8401)
Santiago, Region M. de Santiago, Chile, 8420383
Actively Recruiting
18
Bradford Hill Norte ( Site 8407)
Antofagasta, Chile, 1263521
Actively Recruiting
19
Beijing Cancer hospital-Digestive Oncology ( Site 7500)
Beijing, Beijing Municipality, China, 100142
Actively Recruiting
20
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 7501)
Fuzhou, Fujian, China, 350025
Actively Recruiting
21
The First Affiliated hospital of Xiamen University ( Site 7503)
Xiamen, Fujian, China, 361003
Actively Recruiting
22
Henan Cancer Hospital ( Site 7504)
Zhengzhou, Henan, China, 450000
Actively Recruiting
23
The First Affiliated Hospital of Nanchang University ( Site 7514)
Nanchang, Jiangxi, China, 330000
Actively Recruiting
24
Fudan University Shanghai Cancer Center ( Site 7513)
Shanghai, Shanghai Municipality, China, 200032
Actively Recruiting
25
Xinjiang Medical University Cancer Hospital - Urumqi ( Site 7506)
Ürümqi, Xinjiang, China, 841100
Actively Recruiting
26
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 7510)
Hangzhou, Zhejiang, China, 310016
Actively Recruiting
27
Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi ( Site 7104)
Brest, Finistere, France, 29200
Actively Recruiting
28
CIC. ( Site 7100)
Lille, Nord, France, 59037
Actively Recruiting
29
Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 7102)
Paris, Île-de-France Region, France, 75013
Actively Recruiting
30
NCT-Department of Medical Oncology ( Site 8809)
Heidelberg, Baden-Wurttemberg, Germany, 69120
Actively Recruiting
31
Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 8802)
Düsseldorf, North Rhine-Westphalia, Germany, 40225
Actively Recruiting
32
Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 8807)
Hamburg, Germany, 20249
Actively Recruiting
33
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 7207)
Meldola, Emilia-Romagna, Italy, 47014
Actively Recruiting
34
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 7200)
Milan, Lombardy, Italy, 20133
Actively Recruiting
35
Azienda Ospedaliero Universitaria Pisana ( Site 7206)
Pisa, Tuscany, Italy, 56126
Actively Recruiting
36
Ospedale San Raffaele-Oncologia Medica ( Site 7202)
Milan, Italy, 20132
Actively Recruiting
37
Oslo universitetssykehus, Radiumhospitalet ( Site 8501)
Oslo, Norway, 0379
Actively Recruiting
38
Asan Medical Center-Department of Oncology ( Site 7901)
Seoul, South Korea, 05505
Actively Recruiting
39
Samsung Medical Center-Division of Hematology/Oncology ( Site 7900)
Seoul, South Korea, 06351
Actively Recruiting
40
Hôpitaux Universitaires de Genève (HUG) ( Site 8701)
Geneva, Canton of Geneva, Switzerland, 1211
Actively Recruiting
41
Kantonsspital Graubünden-Medizin ( Site 8700)
Chur, Kanton Graubünden, Switzerland, 7000
Actively Recruiting
42
China Medical University Hospital ( Site 8007)
Taichung, Taiwan, 404332
Actively Recruiting
43
National Cheng Kung University Hospital ( Site 8001)
Tainan, Taiwan, 704
Actively Recruiting
44
National Taiwan University Hospital-Oncology ( Site 8000)
Taipei, Taiwan, 10048
Actively Recruiting
45
Taipei Veterans General Hospital ( Site 8005)
Taipei, Taiwan, 112
Actively Recruiting
Research Team
T
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How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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