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

NCT06445972 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 3475-06D2023-509306-29-00U1111-1299-8160MK-3475-06D
• Study Type: interventional
• Target: 210
• Locations: 11 countries
• Sites: 45

Brief Summary

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, and HER3-DXD plus ramucirumab 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.

Conditions

Gastroesophageal Junction; Gastroesophageal Adenocarcinoma; Esophageal Neoplasms; Esophageal Cancer

Keywords

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)

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase

  DLTs are defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The percentage of participants who experience at least one DLT will be presented.

  Up to ~28 days

• Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In Phase

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.

  Up to ~60 days

• Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study intervention due to an AE will be presented.

  Up to ~28 days

• Objective Response Rate (ORR)

  ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

  Up to ~28 months

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  Up to ~50 months

• Duration of Response (DOR)

  Up to ~50 months

• Overall Survival (OS)

  Up to ~50 months

• Percentage of Particiapants who Experience an AE During the Efficacy Phase

  Up to ~50 months

• Percentage of Participants who Discontinue Study Intervention Due to an AE During the Efficacy Phase

  Up to ~50 months

Study Arms (3)

Ramucirumab + Paclitaxel

ACTIVE COMPARATOR

Participants 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) until discontinuation.

Biological: Ramucirumab; Drug: Paclitaxel

Sacituzumab Tirumotecan + Paclitaxel

EXPERIMENTAL

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 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) plus sacituzumab tirumotecan at selected dose IV infusion on days 1, 15, 29 of every 6-week cycle until discontinuation.

Drug: Paclitaxel; Biological: Sacituzumab Tirumotecan; Drug: Rescue Medications

HER3-DXd + Ramucirumab

EXPERIMENTAL

Participants receive HER3-DXd via IV infusion on days 1 and 22 of each 6-week cycle plus ramucirumab at 8mg/kg via IV infusion on days 1 and 15 and 29 of each 6-week cycle until discontinuation.

Biological: Ramucirumab; Drug: Rescue Medications; Biological: HER3-DXd

Interventions

Ramucirumab BIOLOGICAL

8 mg/kg IV Infusion

HER3-DXd + Ramucirumab; Ramucirumab + Paclitaxel

Paclitaxel DRUG

80 mg/M\^2 IV infusion

Ramucirumab + Paclitaxel; Sacituzumab Tirumotecan + Paclitaxel

Sacituzumab Tirumotecan BIOLOGICAL

3 mg/kg or 4 mg/kg IV Infusion

Also known as: MK-2870, SKB264, sac-TMT

Sacituzumab Tirumotecan + Paclitaxel

Rescue Medications DRUG

Participants receive rescue medications according to each approved drug's product label. Recommended rescue medications for the Sacituzumab Tirumotecan + Paclitaxel arm include antihistamines (histamine-1 and histamine-2 receptor antagonists), acetaminophen or equivalent, dexamethasone or equivalent infusion, and steroid mouth wash (dexamethasone or equivalent) and rescue medications for the HER3-DXd + ramucirumab arm include 5-HT3-receptor antagonist, NK-1 receptor antagonist, and corticosteroids.

HER3-DXd + Ramucirumab; Sacituzumab Tirumotecan + Paclitaxel

HER3-DXd BIOLOGICAL

IV Infusion

Also known as: patritumab deruxtecan, MK-1022, U3-1402

HER3-DXd + Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has histologically and/or cytologically confirmed diagnosis of previously treated, second line (2L) (received first line (1L) treatment) gastric adenocarcinoma, gastroesophageal junction 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
• Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
• Can provide a core/excisional biopsy of a tumor lesion not previously irradiated (collected from a biopsy performed after the most recent systemic anticancer therapy regimen)
• 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 allocation/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

You may not qualify if:

• 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 allocation/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 allocation/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 allocation/randomization, or central venous access device placement within 7 days prior to allocation/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 or other antiplatelet agents
• Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to allocation/randomization

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (45)

University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 8927)

Tucson, Arizona, 85719, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica ( Site 8905)

Los Angeles, California, 90404, United States

RECRUITING

Norton Cancer Institute - Downtown ( Site 8900)

Louisville, Kentucky, 40202, United States

COMPLETED

The Cancer and Hematology Centers ( Site 8912)

Grand Rapids, Michigan, 49503, United States

RECRUITING

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

East Syracuse, New York, 13057, United States

RECRUITING

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

New York, New York, 10032, United States

COMPLETED

UPMC Hillman Cancer Center-UPMC ( Site 8904)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Texas MD Anderson Cancer Center ( Site 8920)

Houston, Texas, 77030, United States

RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 8303)

Natal, Rio Grande do Norte, 59062-000, Brazil

RECRUITING

Hospital Nossa Senhora da Conceição ( Site 8301)

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

RECRUITING

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

São Paulo, São Paulo, 03102-002, Brazil

RECRUITING

Clínica Puerto Montt ( Site 8409)

Port Montt, Los Lagos Region, 5500243, Chile

RECRUITING

Centro de Investigación del Maule ( Site 8408)

Talca, Maule Region, 3481349, Chile

RECRUITING

FALP-UIDO ( Site 8400)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Oncología de Precisión-Oncology ( Site 8404)

Santiago, Region M. de Santiago, 7560908, Chile

RECRUITING

Clínica UC San Carlos de Apoquindo ( Site 8405)

Santiago, Region M. de Santiago, 7620002, Chile

RECRUITING

Bradfordhill-Clinical Area ( Site 8401)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Bradford Hill Norte ( Site 8407)

Antofagasta, 1263521, Chile

RECRUITING

Beijing Cancer hospital-Digestive Oncology ( Site 7500)

Beijing, Beijing Municipality, 100142, China

RECRUITING

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

Fuzhou, Fujian, 350025, China

RECRUITING

The First Affiliated hospital of Xiamen University ( Site 7503)

Xiamen, Fujian, 361003, China

RECRUITING

Henan Cancer Hospital ( Site 7504)

Zhengzhou, Henan, 450000, China

RECRUITING

The First Affiliated Hospital of Nanchang University ( Site 7514)

Nanchang, Jiangxi, 330000, China

RECRUITING

Fudan University Shanghai Cancer Center ( Site 7513)

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Xinjiang Medical University Cancer Hospital - Urumqi ( Site 7506)

Ürümqi, Xinjiang, 841100, China

RECRUITING

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

Hangzhou, Zhejiang, 310016, China

RECRUITING

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

Brest, Finistere, 29200, France

RECRUITING

CIC. ( Site 7100)

Lille, Nord, 59037, France

RECRUITING

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

Paris, Île-de-France Region, 75013, France

RECRUITING

NCT-Department of Medical Oncology ( Site 8809)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

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

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 8807)

Hamburg, 20249, Germany

RECRUITING

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

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

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

Milan, Lombardy, 20133, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana ( Site 7206)

Pisa, Tuscany, 56126, Italy

RECRUITING

Ospedale San Raffaele-Oncologia Medica ( Site 7202)

Milan, 20132, Italy

RECRUITING

Oslo universitetssykehus, Radiumhospitalet ( Site 8501)

Oslo, 0379, Norway

RECRUITING

Asan Medical Center-Department of Oncology ( Site 7901)

Seoul, 05505, South Korea

RECRUITING

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

Seoul, 06351, South Korea

RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 8701)

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Kantonsspital Graubünden-Medizin ( Site 8700)

Chur, Kanton Graubünden, 7000, Switzerland

RECRUITING

China Medical University Hospital ( Site 8007)

Taichung, 404332, Taiwan

RECRUITING

National Cheng Kung University Hospital ( Site 8001)

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital-Oncology ( Site 8000)

Taipei, 10048, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 8005)

Taipei, 112, Taiwan

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Ramucirumab; Paclitaxel; patritumab deruxtecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: August 7, 2024
• Primary Completion (Estimated): May 9, 2028
• Study Completion (Estimated): August 8, 2030
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

IT (4); FR (3); DE (3); KR (2); TW (4); US (8); BR (3); CL (7); CN (8); CH (2); NO (1)