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)

May 21, 2026 updated by: Merck Sharp & Dohme LLC

A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With 1L Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma): Substudy 06C

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The master protocol is MK-3475-U06.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
      • São Paulo, Brazil, 03102-006
        • Recruiting
        • IBCC - Instituto Brasileiro de Controle do Câncer ( Site 6304)
        • Contact:
          • Study Coordinator
          • Phone Number: 551144500300
      • São Paulo, Brazil, 01246-000
        • Recruiting
        • ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 6300)
        • Contact:
          • Study Coordinator
          • Phone Number: 551138932000
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062-000
        • Recruiting
        • Liga Norte Riograndense Contra o Câncer ( Site 6303)
        • Contact:
          • Study Coordinator
          • Phone Number: +558440095595
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
        • Recruiting
        • Hospital Nossa Senhora da Conceição ( Site 6301)
        • Contact:
          • Study Coordinator
          • Phone Number: +5551993590437
  • Chile
      • Antofagasta, Chile, 1263521
        • Recruiting
        • Bradford Hill Norte ( Site 6407)
        • Contact:
          • Study Coordinator
          • Phone Number: 56442023631
    • Los Lagos Region
      • Port Montt, Los Lagos Region, Chile, 5500243
        • Recruiting
        • Clínica Puerto Montt ( Site 6409)
        • Contact:
          • Study Coordinator
          • Phone Number: 56961687093
    • Maule Region
      • Talca, Maule Region, Chile, 3481349
        • Recruiting
        • Centro de Investigación del Maule ( Site 6408)
        • Contact:
          • Study Coordinator
          • Phone Number: 56712981241
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 7500921
        • Recruiting
        • FALP-UIDO ( Site 6400)
        • Contact:
          • Study Coordinator
          • Phone Number: 56224205098
      • Santiago, Region M. de Santiago, Chile, 7560908
        • Recruiting
        • Centro de Oncología de Precisión-Oncology ( Site 6404)
        • Contact:
          • Study Coordinator
          • Phone Number: 56225189885
      • Santiago, Region M. de Santiago, Chile, 7620002
        • Recruiting
        • Clínica UC San Carlos de Apoquindo ( Site 6405)
        • Contact:
          • Study Coordinator
          • Phone Number: 56934271024
      • Santiago, Region M. de Santiago, Chile, 8420383
        • Recruiting
        • Bradfordhill-Clinical Area ( Site 6401)
        • Contact:
          • Study Coordinator
          • Phone Number: 56229490970
  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Recruiting
        • Beijing Cancer hospital-Digestive Oncology ( Site 5500)
        • Contact:
          • Study Coordinator
          • Phone Number: (010)88196317
    • Fujian
      • Fuzhou, Fujian, China, 350025
        • Recruiting
        • The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Site 5501)
        • Contact:
          • Study Coordinator
          • Phone Number: 0591-22859606
      • Xiamen, Fujian, China, 361003
        • Recruiting
        • The First Affiliated hospital of Xiamen University ( Site 5503)
        • Contact:
          • Study Coordinator
          • Phone Number: 0592-2139767
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Recruiting
        • Henan Cancer Hospital ( Site 5504)
        • Contact:
          • Study Coordinator
          • Phone Number: 400-0371-818
    • Jiangxi
      • Nanchang, Jiangxi, China, 330000
        • Recruiting
        • The First Affiliated Hospital of Nanchang University ( Site 5514)
        • Contact:
          • Study Coordinator
          • Phone Number: 0791-86427234
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center ( Site 5513)
        • Contact:
          • Study Coordinator
          • Phone Number: （021）6417 5590
    • Xinjiang
      • Ürümqi, Xinjiang, China, 841100
        • Recruiting
        • Xinjiang Medical University Cancer Hospital - Urumqi ( Site 5506)
        • Contact:
          • Study Coordinator
          • Phone Number: (+86) 0991-7819113
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
        • Recruiting
        • Sir Run Run Shaw Hospital of Zhejiang University School of Medicine ( Site 5510)
        • Contact:
          • Study Coordinator
          • Phone Number: 0571 8609 0073
  • France
    • Finistere
      • Brest, Finistere, France, 29200
        • Recruiting
        • CHU-BREST Cavale Blanche ( Site 5104)
        • Contact:
          • Study Coordinator
          • Phone Number: 33298223428
    • Nord
      • Lille, Nord, France, 59037
        • Recruiting
        • CIC. ( Site 5100)
        • Contact:
          • Study Coordinator
          • Phone Number: +33320445461
    • Île-de-France Region
      • Paris, Île-de-France Region, France, 75013
        • Recruiting
        • Pitie Salpetriere University Hospital-Hepato-Gastro-Enterology ( Site 5102)
        • Contact:
          • Study Coordinator
          • Phone Number: +331 42 16 10 41
  • Germany
      • Hamburg, Germany, 20249
        • Recruiting
        • Facharztzentrum Eppendorf-Facharztzentrum Eppendorf ( Site 6807)
        • Contact:
          • Study Coordinator
          • Phone Number: + 4940360352246
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • Recruiting
        • NCT-Department of Medical Oncology ( Site 6809)
        • Contact:
          • Study Coordinator
          • Phone Number: +49 62215637784
    • North Rhine-Westphalia
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
        • Recruiting
        • Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 6802)
        • Contact:
          • Study Coordinator
          • Phone Number: +492118108751
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Recruiting
        • Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 6806)
        • Contact:
          • Study Coordinator
          • Phone Number: +49351 458 11750
  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele-Oncologia Medica ( Site 5202)
        • Contact:
          • Study Coordinator
          • Phone Number: +390226437615
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Recruiting
        • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 5207)
        • Contact:
          • Study Coordinator
          • Phone Number: 0543739100
    • Lombardy
      • Milan, Lombardy, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 5200)
        • Contact:
          • Study Coordinator
          • Phone Number: 0223903807
    • Tuscany
      • Pisa, Tuscany, Italy, 56126
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana ( Site 5206)
        • Contact:
          • Study Coordinator
          • Phone Number: 050992454
  • Norway
      • Oslo, Norway, 0379
        • Recruiting
        • Oslo universitetssykehus, Radiumhospitalet ( Site 6501)
        • Contact:
          • Study Coordinator
          • Phone Number: 4723026600
  • South Korea
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center-Department of Oncology ( Site 5901)
        • Contact:
          • Study Coordinator
          • Phone Number: +82230103217
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center-Division of Hematology/Oncology ( Site 5900)
        • Contact:
          • Study Coordinator
          • Phone Number: 82234101795
  • Switzerland
    • Canton of Geneva
      • Geneva, Canton of Geneva, Switzerland, 1211
        • Recruiting
        • Hôpitaux Universitaires de Genève (HUG) ( Site 6701)
        • Contact:
          • Study Coordinator
          • Phone Number: +41 22 372 29 01
    • Kanton Graubünden
      • Chur, Kanton Graubünden, Switzerland, 7000
        • Recruiting
        • Kantonsspital Graubünden-Medizin ( Site 6700)
        • Contact:
          • Study Coordinator
          • Phone Number: +41 81 256 61 11
  • Taiwan
      • Taichung, Taiwan, 404
        • Recruiting
        • China Medical University Hospital ( Site 6007)
        • Contact:
          • Study Coordinator
          • Phone Number: 886422052121x15057
      • Tainan, Taiwan, 704
        • Recruiting
        • National Cheng Kung University Hospital ( Site 6001)
        • Contact:
          • Study Coordinator
          • Phone Number: +88662353535x4559
      • Taipei, Taiwan, 10048
        • Recruiting
        • National Taiwan University Hospital-Oncology ( Site 6000)
        • Contact:
          • Study Coordinator
          • Phone Number: +88623123456x267852
      • Taipei, Taiwan, 112
        • Recruiting
        • Taipei Veterans General Hospital ( Site 6005)
        • Contact:
          • Study Coordinator
          • Phone Number: +88628717270x131
  • Thailand
    • Bangkok
      • Bangkoknoi, Bangkok, Thailand, 10700
        • Recruiting
        • Faculty of Medicine Siriraj Hospital ( Site 6102)
        • Contact:
          • Study Coordinator
          • Phone Number: +6624194489
      • Pathumwan, Bangkok, Thailand, 10330
        • Recruiting
        • Chulalongkorn Hospital ( Site 6104)
        • Contact:
          • Study Coordinator
          • Phone Number: 022564533
      • Ratchathewi, Bangkok, Thailand, 10400
        • Recruiting
        • Ramathibodi Hospital ( Site 6103)
        • Contact:
          • Study Coordinator
          • Phone Number: 022011671
    • Changwat Songkhla
      • Hat Yai, Changwat Songkhla, Thailand, 90110
        • Recruiting
        • Songklanagarind hospital ( Site 6101)
        • Contact:
          • Study Coordinator
          • Phone Number: +6674451469
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 6927)
        • Contact:
          • Study Coordinator
          • Phone Number: 520-621-2449
    • California
      • Los Angeles, California, United States, 90404
        • Recruiting
        • UCLA Hematology/Oncology - Santa Monica ( Site 6905)
        • Contact:
          • Study Coordinator
          • Phone Number: 310-570-1453
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Completed
        • Norton Hospital-Norton Cancer Institute - Downtown ( Site 6900)
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • The Cancer and Hematology Centers ( Site 6912)
        • Contact:
          • Study Coordinator
          • Phone Number: 616-975-3065
    • New York
      • East Syracuse, New York, United States, 13057
        • Recruiting
        • Hematology-Oncology Associates of Central NY, P.C. ( Site 6925)
        • Contact:
          • Study Coordinator
          • Phone Number: 315-472-7504
      • New York, New York, United States, 10032
        • Completed
        • Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 6907)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center-UPMC ( Site 6904)
        • Contact:
          • Study Coordinator
          • Phone Number: 816-898-9413
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center ( Site 6920)
        • Contact:
          • Study Coordinator
          • Phone Number: 833-589-0868

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

  • Has histologically and/or cytologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic first-line (1L) gastroesophageal adenocarcinoma
  • Is not expected to require tumor resection during the treatment course
  • Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines
  • Core/excisional biopsy of a tumor lesion not previously irradiated has been provided
  • Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
  • Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy are eligible
  • Has adequate organ function
  • Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment and verified by blinded independent central review (BICR)
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the first dose of study intervention
  • Has a life expectancy of at least 6 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

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

  • Has squamous cell or undifferentiated gastroesophageal cancer.
  • Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma
  • Has experienced weight loss >20% over 3 months before the first dose of study intervention
  • Has a 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 uncontrolled, significant cardiovascular disease or cerebrovascular disease within 6 months preceding study intervention
  • Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
  • Has history of human immunodeficiency virus (HIV) infection with Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted or anti-human epidermal growth factor receptor 3 (HER3) targeted agents
  • Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC) and/or a topoisomerase I inhibitor-based chemotherapy
  • Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention
  • Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)
  • 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
  • Has received a strong inducer/inhibitor of CYP3A4 that cannot be discontinued
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
  • Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
  • Has known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has Severe hypersensitivity (≥Grade 3) to pembrolizumab, sacituzumab tirumotecan, patritumab deruxtecan, or other biologic therapy, chemotherapy (ie, oxaliplatin, fluorouracil, capecitabine), leucovorin, levoleucovorin, or any of their excipients
  • Has active autoimmune disease that has required systemic treatment in the past 2 years
  • Has history of (noninfectious) pneumonitis or interstitial lung disease (ILD) that required steroids or has current pneumonitis or ILD, or where suspected ILD or pneumonitis cannot be ruled out by imaging at screening
  • Has an active infection requiring systemic therapy
  • Has concurrent active hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable HBV DNA) and hepatitis C virus (defined as anti-hepatitis C virus [HCV] Ab positive and detectable HCV ribonucleic acid [RNA] infection or a known history of hepatitis B and/or C infection
  • Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study
  • Has gastrointestinal (GI) obstruction, poor oral intake, or difficulty in taking oral medication
  • Has poorly controlled diarrhea
  • Has had a major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention
  • Has history of allogeneic tissue/solid organ transplant
  • Has not adequately recovered from major surgery or has ongoing surgical complications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pembrolizumab plus Chemotherapy
Participants will receive pembrolizumab 400 mg via intravenous (IV) injection on day 1 of every 6 week cycle (Q6W) for up to 18 cycles (up to ~2 years) AND investigator's choice of CAPOX chemotherapy (capecitabine 1000 mg/m^2 orally twice daily for 14 days every 3 weeks (Q3W) and oxaliplatin 130 mg/m^2 via IV infusion Q3W) OR mFOLFOX6 chemotherapy (oxaliplatin 85 mg/m^2 via IV infusion Q3W; 5-Fluorouracil (5-FU) 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once every 2 weeks (Q2W); and leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W).
Biological: Pembrolizumab
Administered via intravenous (IV) infusion.
Other Names:
  • MK-3475
  • Keytruda®
Drug: Capecitabine
Administered via oral tablet.
Other Names:
  • XELODA
Drug: Leucovorin
Administered via IV infusion.
Other Names:
  • folinic acid
  • WELLCOVORIN®
  • calcium folinate
Drug: Levoleucovorin
Administered via IV infusion.
Other Names:
  • FUSILEV®
  • calcium levofolinate
  • levofolinic acid
Drug: 5-Fluorouracil (5-FU)
Administered via IV infusion
Other Names:
  • ADRUCIL®
Drug: Oxaliplatin
Administered via IV infusion
Experimental: Pembrolizumab plus Sacituzumab Tirumotecan plus Chemotherapy
Participants will receive sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to ~2 years) AND investigator's choice of capecitabine 1000 mg/m^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once Q2W AND leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W.
Biological: Pembrolizumab
Administered via intravenous (IV) infusion.
Other Names:
  • MK-3475
  • Keytruda®
Drug: Capecitabine
Administered via oral tablet.
Other Names:
  • XELODA
Drug: Leucovorin
Administered via IV infusion.
Other Names:
  • folinic acid
  • WELLCOVORIN®
  • calcium folinate
Drug: Levoleucovorin
Administered via IV infusion.
Other Names:
  • FUSILEV®
  • calcium levofolinate
  • levofolinic acid
Biological: Sacituzumab Tirumotecan (sac-TMT)
Administered via IV infusion.
Other Names:
  • SKB264
  • MK-2870
Drug: 5-Fluorouracil (5-FU)
Administered via IV infusion
Other Names:
  • ADRUCIL®
Experimental: Pembrolizumab plus Patritumab Deruxtecan plus Chemotherapy
Participants will receive patritumab deruxtecan via IV infusion on Days 1 and 22 Q6W until discontinuation, pembrolizumab 400 mg via IV injection on day 1 Q6W for up to 18 cycles (up to ~2 years) AND investigator's choice of capecitabine 1000 mg/m^2 orally twice daily for 14 days Q3W OR 5-FU 400 mg/^2 via bolus IV plus 2400 mg/m^2 continuous IV once Q2W AND leucovorin 400 mg/m^2 via IV infusion Q2W OR levoleucovorin 200 mg/m^2 Q2W.
Biological: Pembrolizumab
Administered via intravenous (IV) infusion.
Other Names:
  • MK-3475
  • Keytruda®
Drug: Capecitabine
Administered via oral tablet.
Other Names:
  • XELODA
Drug: Leucovorin
Administered via IV infusion.
Other Names:
  • folinic acid
  • WELLCOVORIN®
  • calcium folinate
Drug: Levoleucovorin
Administered via IV infusion.
Other Names:
  • FUSILEV®
  • calcium levofolinate
  • levofolinic acid
Drug: 5-Fluorouracil (5-FU)
Administered via IV infusion
Other Names:
  • ADRUCIL®
Biological: Patritumab Deruxtecan
Administered via IV infusion
Other Names:
  • U3-1402
  • HER3-DXd
  • MK-1022

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Lead-in Phase: Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLTs)
Time Frame: Up to approximately 28 days
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 reported.
Up to approximately 28 days
Safety Lead-in Phase: Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 28 days
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 28 days
Safety Lead-in Phase: Number of Participants Who Discontinued Study Intervention Due to an AE
Time Frame: Up to approximately 28 days
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 28 days
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: Up to approximately 28 months
ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Up to approximately 28 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR
Time Frame: Up to approximately 55 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Up to approximately 55 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time Frame: Up to approximately 55 months
For participants who demonstrate a confirmed 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 RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Up to approximately 55 months
Overall Survival (OS)
Time Frame: Up to approximately 55 months
OS is defined as the time from randomization to the date of death from any cause.
Up to approximately 55 months
Number of Participants Who Experience an Adverse Event (AE)
Time Frame: Up to approximately 55 months
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 55 months
Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 55 months
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 55 months
Incidence of Antidrug Antibodies (ADA) to investigational agents - (sacituzumab tirumotecan (sac-TMT, MK-2870) and patritumab deruxtecan (HER3-DXd))
Time Frame: At designated timepoints up to approximately 55 months
Blood samples collected at designated timepoints will be used to determine the ADA response to investigational agents. The incidence of ADAs over time will be presented.
At designated timepoints up to approximately 55 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2024

Primary Completion (Estimated)

September 12, 2029

Study Completion (Estimated)

September 12, 2029

Study Registration Dates

First Submitted

June 17, 2024

First Submitted That Met QC Criteria

June 17, 2024

First Posted (Actual)

June 24, 2024

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 21, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-06C
  • MK-3475-06C (Other Identifier: MSD)
  • KEYMAKER-06C (Other Identifier: MSD)
  • U1111-1299-8084 (Registry Identifier: UTN)
  • 2023-509307-33-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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