KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)

May 15, 2026 updated by: Merck Sharp & Dohme LLC

KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC.

This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Study Type

Interventional

Enrollment (Estimated)

450

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

  • Hungary
      • Budapest, Hungary, 1121
        • Completed
        • Országos Korányi Pulmonológiai Intézet ( Site 0060)
    • Győr-Moson-Sopron
      • Győr, Győr-Moson-Sopron, Hungary, 9024
        • Completed
        • Petz Aladar Megyei Oktato Korhaz ( Site 0062)
    • Jász-Nagykun-Szolnok
      • Szolnok, Jász-Nagykun-Szolnok, Hungary, 5004
        • Completed
        • Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
  • Israel
      • Beersheba, Israel, 8457108
        • Completed
        • Soroka Medical Center ( Site 0072)
      • Haifa, Israel, 3109601
        • Completed
        • Rambam Health Care Campus-Oncology ( Site 0076)
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center ( Site 0075)
        • Contact:
          • Study Coordinator
          • Phone Number: +97225645203
      • Kfar Saba, Israel, 4428132
        • Completed
        • Meir Medical Center ( Site 0071)
      • Petah Tikva, Israel, 4941492
        • Completed
        • Rabin Medical Center ( Site 0074)
      • Ramat Gan, Israel, 5262000
        • Recruiting
        • Chaim Sheba Medical Center ( Site 0070)
        • Contact:
          • Study Coordinator
          • Phone Number: +97235307096
      • Tel Aviv, Israel, 6423906
        • Completed
        • Sourasky Medical Center ( Site 0077)
  • Italy
      • Milan, Italy, 20132
        • Completed
        • IRCCS Ospedale San Raffaele ( Site 0171)
      • Roma, Italy, 00168
        • Completed
        • Policlinico Gemelli di Roma ( Site 0174)
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Completed
        • Azienda Ospedaliera Universitaria Careggi ( Site 0173)
  • Poland
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Active, not recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 0151)
    • Pomeranian Voivodeship
      • Gdansk, Pomeranian Voivodeship, Poland, 80-952
        • Active, not recruiting
        • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
    • West Pomeranian Voivodeship
      • Koszalin, West Pomeranian Voivodeship, Poland, 75-581
        • Active, not recruiting
        • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
  • South Korea
      • Seoul, South Korea, 03722
        • Completed
        • Severance Hospital ( Site 0080)
      • Seoul, South Korea, 06351
        • Completed
        • Samsung Medical Center ( Site 0082)
    • Kyonggi-do
      • Seongnam-si, Kyonggi-do, South Korea, 13620
        • Completed
        • Seoul National University Bundang Hospital ( Site 0081)
  • Spain
      • Madrid, Spain, 28223
        • Active, not recruiting
        • Hospital Universitario Quiron Madrid ( Site 0091)
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Active, not recruiting
        • ICO L Hospitalet ( Site 0090)
  • Taiwan
      • Changhua, Taiwan, 50006
        • Recruiting
        • Changhua Christian Hospital ( Site 0181)
        • Contact:
          • Study Coordinator
          • Phone Number: +886983901629
      • Taipei, Taiwan, 110301
        • Recruiting
        • Taipei Medical University Hospital ( Site 0180)
        • Contact:
          • Study Coordinator
          • Phone Number: +886227372181x7810
      • Taoyuan, Taiwan, 33305
        • Recruiting
        • Chang Gung Medical Foundation-Linkou Branch ( Site 0182)
        • Contact:
          • Study Coordinator
          • Phone Number: +886975368109
  • Ukraine
    • Cherkasy Oblast
      • Cherkasy, Cherkasy Oblast, Ukraine, 18009
        • Recruiting
        • COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0463)
        • Contact:
          • Study Coordinator
          • Phone Number: +380472370123
    • Ivano-Frankivsk Oblast
      • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
        • Recruiting
        • Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site 0460)
        • Contact:
          • Study Coordinator
          • Phone Number: +380978411455
    • Rivne Oblast
      • Rivne, Rivne Oblast, Ukraine, 33010
        • Recruiting
        • ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0461)
        • Contact:
          • Study Coordinator
          • Phone Number: +380362633075
    • Zakarpattia Oblast
      • Uzhhorod, Zakarpattia Oblast, Ukraine, 88000
        • Recruiting
        • Uzhhorod Multispecialty City Clinical Hospital ( Site 0462)
        • Contact:
          • Study Coordinator
          • Phone Number: +380506847086
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Active, not recruiting
        • Banner MD Anderson Cancer Center ( Site 0001)
    • California
      • Duarte, California, United States, 91010
        • Completed
        • City of Hope ( Site 0014)
      • San Francisco, California, United States, 94158
        • Completed
        • UCSF Medical Center at Mission Bay ( Site 0007)
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Completed
        • Georgetown University ( Site 0036)
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0293
        • Completed
        • University of Kentucky Markey Cancer Center ( Site 0019)
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Completed
        • MedStar Franklin Square Medical Center ( Site 0033)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Completed
        • Massachusetts General Hospital ( Site 0003)
      • Boston, Massachusetts, United States, 02215
        • Completed
        • Dana Farber Cancer Institute ( Site 0002)
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Completed
        • Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03766
        • Recruiting
        • Dartmouth Hitchcock Medical Center ( Site 0016)
        • Contact:
          • Study Coordinator
          • Phone Number: 603-650-4428
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Completed
        • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
    • New York
      • New York, New York, United States, 10016
        • Completed
        • Laura and Isaac Perlmutter Cancer Center ( Site 0034)
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Recruiting
        • Sanford Fargo Medical Center ( Site 0039)
        • Contact:
          • Study Coordinator
          • Phone Number: 701-234-2000
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Completed
        • Cleveland Clinic Main ( Site 0006)
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0015)
        • Contact:
          • Study Coordinator
          • Phone Number: 614-366-0233
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
        • Contact:
          • Study Coordinator
          • Phone Number: 215-220-9703
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Recruiting
        • Sanford Cancer Center ( Site 0038)
        • Contact:
          • Study Coordinator
          • Phone Number: 605-328-8000
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center ( Site 0009)
        • Contact:
          • Study Coordinator
          • Phone Number: 713-792-6363

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

  • Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
  • Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
  • Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
  • Has not received prior systemic treatment for their metastatic NSCLC
  • Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B

Exclusion Criteria:

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

  • Has a diagnosis of small cell lung cancer
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
  • Has a known history of human immunodeficiency virus (HIV) infection. Well-controlled HIV with anti-retroviral therapy (ART) is not excluded
  • Has a known history of Hepatitis B (HPV) or known active Hepatitis C virus infection. Hepatitis B surface antigen (HBsAg) positive is eligible if on HBV antiviral therapy for at least 4 weeks and HBV viral load is undetectable prior to randomization
  • Has had major surgery <3 weeks before the first dose of study treatment
  • Is expected to require any other form of antineoplastic therapy while on study
  • Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
  • Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
  • Has preexisting neuropathy that is moderate in intensity
  • Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
  • Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
  • Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
  • Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
  • Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
  • Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
  • Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
  • Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • Has had an allogenic tissue/solid organ transplant

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
Experimental: Part A: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Paclitaxel
IV infusion
Other Names:
  • ABRAXANE®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: Vibostolimab
IV infusion
Other Names:
  • MK-7684
Experimental: Part A: Pembrolizumab+Vibostolimab+Carboplatin + Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Drug: Pemetrexed
IV infusion
Other Names:
  • ALIMTA®
Biological: Vibostolimab
IV infusion
Other Names:
  • MK-7684
Experimental: Part A: Pembrolizumab+Boserolimab+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Paclitaxel
IV infusion
Other Names:
  • ABRAXANE®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: Boserolimab
IV infusion
Other Names:
  • MK-5890
Experimental: Part A: Pembrolizumab+Boserolimab+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m^2 IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Drug: Pemetrexed
IV infusion
Other Names:
  • ALIMTA®
Biological: Boserolimab
IV infusion
Other Names:
  • MK-5890
Experimental: Part A: Pembrolizumab+MK-4830+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Paclitaxel
IV infusion
Other Names:
  • ABRAXANE®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: MK-4830
IV infusion
Experimental: Part A: Pembrolizumab+MK-4830+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Drug: Pemetrexed
IV infusion
Other Names:
  • ALIMTA®
Biological: MK-4830
IV infusion
Experimental: Part A: Pembrolizumab+MK-0482+Carboplatin+Paclitaxel
On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: MK-0482
IV Infusion
Experimental: Part A: Pembrolizumab+MK-0482+Carboplatin+Pemetrexed
On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: MK-0482
IV Infusion
Experimental: Part B: Pembrolizumab + I-DXd
On Day 1 of each 3-week cycle, participants with squamous and nonsquamous NSCLC will receive pembrolizumab 200 mg IV for up to 2 years, PLUS I-DXd in escalating doses until progressive disease or toxicity.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Biological: Ifinatamab Deruxtecan (I-DXd)
IV infusion
Other Names:
  • DS-7300a
  • MK-2400
Experimental: Part B: Pembrolizumab + Carboplatin + I-DXd
On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS I-DXd IV in escalating doses until PD or toxicity.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: Ifinatamab Deruxtecan (I-DXd)
IV infusion
Other Names:
  • DS-7300a
  • MK-2400
Experimental: Part B: Pembrolizumab + Carboplatin + HER3-DXd
On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS HER3-DXd IV in escalating doses until PD or toxicity.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: HER3-DXd
IV Infusion
Other Names:
  • U3-1402
  • MK-1022

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 24 months
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported.
Up to approximately 24 months
Part B: Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame: Up to approximately 27 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported.
Up to approximately 27 months
Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)
Time Frame: Up to approximately 24 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported.
Up to approximately 24 months
Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
Time Frame: Up to approximately 3 Weeks
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.
Up to approximately 3 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Progression-Free Survival (PFS) According to RECIST 1.1
Time Frame: Up to approximately 24 months
PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥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 ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported.
Up to approximately 24 months
Part A: Number of Participants Who Experience One or More AEs
Time Frame: Up to approximately 27 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported.
Up to approximately 27 months
Part A: Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 24 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported.
Up to approximately 24 months
Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR)
Time Frame: Up to approximately 24 months
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported.
Up to approximately 24 months
Part B: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
Time Frame: Up to approximately 24 months
For participants who show confirmed CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported.
Up to approximately 24 months
Part B: Cmax of I-DXd
Time Frame: At designated time points up to approximately 2 years
Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of I-DXd.
At designated time points up to approximately 2 years
Part B: Cmax of HER3-DXd
Time Frame: At designated time points up to approximately 2 years
Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of HER3-DXd.
At designated time points up to approximately 2 years
Part B: Cmax of pembrolizumab
Time Frame: At designated time points up to approximately 2 years
Cmax is the maximum concentration of the drug observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of pembrolizumab.
At designated time points up to approximately 2 years
Part B: Ctrough of I-DXd
Time Frame: At designated time points up to approximately 2 years
Ctrough is defined as the lowest observed concentration of drug in plasma at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of I-DXd.
At designated time points up to approximately 2 years
Part B: Ctrough of HER3-DXd
Time Frame: At designated time points up to approximately 2 years
Ctrough is defined as the lowest observed concentration of drug in plasma at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of HER3-DXd.
At designated time points up to approximately 2 years
Part B: Ctrough of pembrolizumab
Time Frame: At designated time points up to approximately 2 years
Ctrough is defined as the lowest observed concentration of drug in serum at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of pembrolizumab.
At designated time points up to approximately 2 years

Collaborators and Investigators

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

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Daiichi Sankyo

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)

December 19, 2019

Primary Completion (Estimated)

February 13, 2032

Study Completion (Estimated)

February 13, 2032

Study Registration Dates

First Submitted

November 14, 2019

First Submitted That Met QC Criteria

November 14, 2019

First Posted (Actual)

November 15, 2019

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-01A
  • MK-3475-01A (Other Identifier: MSD)
  • KEYMAKER-U01A (Other Identifier: MSD)
  • 2020-001626-56 (EudraCT Number)
  • U1111-1294-6474 (Registry Identifier: UTN)
  • 2023-506932-33-00 (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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