Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

NCT ID: NCT06445972

Last Updated: 2025-11-10

Study Results

Results pending

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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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-07

Study Completion Date

2028-10-27

Brief Summary

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This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Detailed Description

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This is a substudy of the master protocol MK-3475-U06 (KEYMAKER-U06).

Conditions

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Gastroesophageal Junction Gastroesophageal Adenocarcinoma Esophageal Neoplasms Esophageal Cancer

Keywords

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Programmed Cell Death 1 (PD1, PD-1) Programmed Cell Death 1 Ligand 1(PDL1, PD-L1) Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sacituzumab Tirumotecan + Paclitaxel

Following a 28-day run-in with sacituzumab tirumotecan at 3 mg/kg and 4 mg/kg IV infusion on Days 1 and 15 of a 6-week cycle plus paclitaxel at 80 mg/M\^2 IV infusion on days 1, 8 and 15 of a 4-week cycle, participants will receive paclitaxel at 80 mg/M\^2 IV infusion on days 1, 8, 15 of each 4-week cycle (3 weeks on and 1 week off) up to \~60 weeks plus sacituzumab tirumotecan at selected dose IV infusion on days 1, 15, 29 of every 6-week cycle until discontinuation.

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

80 mg/M\^2 IV infusion

Sacituzumab Tirumotecan

Intervention Type BIOLOGICAL

3 mg/kg or 4 mg/kg IV Infusion

Rescue Medications

Intervention Type DRUG

Participants receive rescue medications according to each approved drug's product label. Recommended rescue medications include antihistamines (histamine-1 and histamine-2 receptor antagonists), acetaminophen or equivalent, dexamethasone or equivalent infusion, and steroid mouth wash (dexamethasone or equivalent).

Ramucirumab + Paclitaxel

Participants will receive ramucirumab at 8mg/kg via intravenous (IV) infusion on days 1 and 15 of each 4-week cycle for up to \~60 weeks plus paclitaxel at 80 mg/M\^2 via IV infusion on Days 1, 8, and 15 of each 4-week cycle (3 weeks on and 1 week off) for up to \~60 weeks.

Group Type ACTIVE_COMPARATOR

Ramucirumab

Intervention Type BIOLOGICAL

8 mg/kg IV Infusion

Paclitaxel

Intervention Type DRUG

80 mg/M\^2 IV infusion

Interventions

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Ramucirumab

8 mg/kg IV Infusion

Intervention Type BIOLOGICAL

Paclitaxel

80 mg/M\^2 IV infusion

Intervention Type DRUG

Sacituzumab Tirumotecan

3 mg/kg or 4 mg/kg IV Infusion

Intervention Type BIOLOGICAL

Rescue Medications

Participants receive rescue medications according to each approved drug's product label. Recommended rescue medications include antihistamines (histamine-1 and histamine-2 receptor antagonists), acetaminophen or equivalent, dexamethasone or equivalent infusion, and steroid mouth wash (dexamethasone or equivalent).

Intervention Type DRUG

Other Intervention Names

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MK-2870 SKB264 sac-TMT

Eligibility Criteria

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Inclusion Criteria

* Has histologically and/or cytologically confirmed diagnosis of previously treated, 2L (received first line (1L) treatment) gastric adenocarcinoma, GEJ adenocarcinoma, or esophageal adenocarcinoma
* Has metastatic disease or locally advanced, unresectable disease
* Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy
* Participants with gastroesophageal adenocarcinoma that is known to be human epidermal growth factor receptor 2 (HER2)/neu positive are excluded. Participants with unknown HER2 status are eligible.
* Has provided an archival tumor tissue sample or most recently obtained core, incisional, or excisional biopsy of a tumor lesion
* AEs due to previous anticancer therapies must be ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable.
* Has Eastern Cooperative Oncology Group performance status of 0 or 1
* Has a life expectancy of at least 3 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 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 squamous cell or undifferentiated gastroesophageal cancer
* Has experienced weight loss \>20% over 3 months before the first dose of study intervention
* Has 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 a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days prior to randomization
* Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization
* Has uncontrolled arterial hypertension ≥150/≥90 mm mercury (Hg)
* Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
* Has undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization or planned major surgery following initiation of study treatment
* Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents
* Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs) or other antiplatelet agents
* Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization
* Has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry
* Has history of GI perforation and/or fistulae within 6 months prior to randomization
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC), topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1 inhibitor-based chemotherapy
* Has received any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study drug intervention
* 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. Administration of killed vaccines is allowed
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring systemic therapy
* Has a concurrent active HBV (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid) infection
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has severe hypersensitivity (Grade ≥3) to sacituzumab tirumotecan, any of its excipients and/or to another biologic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

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 8927)

Tucson, Arizona, United States

Site Status RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 8905)

Los Angeles, California, United States

Site Status RECRUITING

Norton Cancer Institute - Downtown ( Site 8900)

Louisville, Kentucky, United States

Site Status RECRUITING

The Cancer and Hematology Centers ( Site 8912)

Grand Rapids, Michigan, United States

Site Status RECRUITING

Hematology-Oncology Associates of Central NY, P.C. ( Site 8925)

East Syracuse, New York, United States

Site Status RECRUITING

Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 8907)

New York, New York, United States

Site Status COMPLETED

UPMC Hillman Cancer Center-UPMC ( Site 8904)

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Texas MD Anderson Cancer Center ( Site 8920)

Houston, Texas, United States

Site Status RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 8303)

Natal, Rio Grande do Norte, Brazil

Site Status RECRUITING

Hospital Nossa Senhora da Conceição ( Site 8301)

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

IBCC - Instituto Brasileiro de Controle do Câncer ( Site 8304)

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Clínica Puerto Montt ( Site 8409)

Port Montt, Los Lagos Region, Chile

Site Status RECRUITING

Centro de Investigación del Maule ( Site 8408)

Talca, Maule Region, Chile

Site Status RECRUITING

FALP-UIDO ( Site 8400)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Centro de Oncología de Precisión-Oncology ( Site 8404)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Clínica UC San Carlos de Apoquindo ( Site 8405)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Bradfordhill-Clinical Area ( Site 8401)

Santiago, Region M. de Santiago, Chile

Site Status RECRUITING

Bradford Hill Norte ( Site 8407)

Antofagasta, , Chile

Site Status RECRUITING

Beijing Cancer hospital-Digestive Oncology ( Site 7500)

Beijing, Beijing Municipality, China

Site Status RECRUITING

The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 7501)

Fuzhou, Fujian, China

Site Status RECRUITING

The First Affiliated hospital of Xiamen University ( Site 7503)

Xiamen, Fujian, China

Site Status RECRUITING

Henan Cancer Hospital ( Site 7504)

Zhengzhou, Henan, China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University ( Site 7514)

Nanchang, Jiangxi, China

Site Status RECRUITING

Fudan University Shanghai Cancer Center ( Site 7513)

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Xinjiang Medical University Cancer Hospital - Urumqi ( Site 7506)

Ürümqi, Xinjiang, China

Site Status RECRUITING

Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 7510)

Hangzhou, Zhejiang, China

Site Status RECRUITING

Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi ( Site 7104)

Brest, Finistere, France

Site Status RECRUITING

CIC. ( Site 7100)

Lille, Nord, France

Site Status RECRUITING

Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 7102)

Paris, Île-de-France Region, France

Site Status RECRUITING

Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 8802)

Düsseldorf, North Rhine-Westphalia, Germany

Site Status RECRUITING

Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 8807)

Hamburg, , Germany

Site Status RECRUITING

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 7207)

Meldola, Emilia-Romagna, Italy

Site Status RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 7200)

Milan, Lombardy, Italy

Site Status RECRUITING

Oslo universitetssykehus, Radiumhospitalet ( Site 8501)

Oslo, , Norway

Site Status RECRUITING

Asan Medical Center-Department of Oncology ( Site 7901)

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center-Division of Hematology/Oncology ( Site 7900)

Seoul, , South Korea

Site Status RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 8701)

Geneva, Canton of Geneva, Switzerland

Site Status RECRUITING

Kantonsspital Graubünden-Medizin ( Site 8700)

Chur, Kanton Graubünden, Switzerland

Site Status RECRUITING

China Medical University Hospital ( Site 8007)

Taichung, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital ( Site 8001)

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital-Oncology ( Site 8000)

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital ( Site 8005)

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Brazil Chile China France Germany Italy Norway South Korea Switzerland Taiwan

Central Contacts

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Toll Free Number

Role: CONTACT

Phone: 1-888-577-8839

Email: [email protected]

Facility Contacts

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Study Coordinator

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Related Links

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Other Identifiers

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2023-509306-29-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1299-8160

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-06D

Identifier Type: OTHER

Identifier Source: secondary_id

3475-06D

Identifier Type: -

Identifier Source: org_study_id