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RecruitingInterventionalPhase 1/Phase 2

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)

NCT ID: NCT04165070Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-16

Summary

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).

Detailed description

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

Arms & interventions

  • BiologicalPembrolizumab

    IV infusion

  • DrugCarboplatin

    IV infusion

  • DrugPaclitaxel

    IV infusion

  • DrugPemetrexed

    IV infusion

  • BiologicalVibostolimab

    IV infusion

  • BiologicalBoserolimab

    IV infusion

  • BiologicalMK-4830

    IV infusion

  • BiologicalMK-0482

    IV Infusion

  • BiologicalIfinatamab Deruxtecan (I-DXd)

    IV infusion

  • BiologicalHER3-DXd

    IV Infusion

Outcome measures

Primary

  • Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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.

    Time frame: Up to approximately 24 months

  • Part B: Number of Participants Who Experience One or More Adverse Events (AEs)

    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.

    Time frame: Up to approximately 27 months

  • Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)

    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.

    Time frame: Up to approximately 24 months

  • Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

    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.

    Time frame: Up to approximately 3 Weeks

Secondary

  • Part A: Progression-Free Survival (PFS) According to RECIST 1.1

    Time frame: Up to approximately 24 months

  • Part A: Number of Participants Who Experience One or More AEs

    Time frame: 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

  • Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR)

    Time frame: 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

  • Part B: Cmax of I-DXd

    Time frame: 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

  • Part B: Cmax of pembrolizumab

    Time frame: 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

  • Part B: Ctrough of HER3-DXd

    Time frame: 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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (18)

Banner MD Anderson Cancer Center ( Site 0001)

Gilbert, Arizona, 85234

Active Not Recruiting

City of Hope ( Site 0014)

Duarte, California, 91010

Completed

UCSF Medical Center at Mission Bay ( Site 0007)

San Francisco, California, 94158

Completed

Georgetown University ( Site 0036)

Washington D.C., District of Columbia, 20007

Completed

University of Kentucky Markey Cancer Center ( Site 0019)

Lexington, Kentucky, 40536-0293

Completed

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237

Completed

Massachusetts General Hospital ( Site 0003)

Boston, Massachusetts, 02114

Completed

Dana Farber Cancer Institute ( Site 0002)

Boston, Massachusetts, 02215

Completed

Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)

Omaha, Nebraska, 68130

Completed

Dartmouth Hitchcock Medical Center ( Site 0016)

Lebanon, New Hampshire, 03766

Recruiting
Study Coordinator · Contact

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)

Hackensack, New Jersey, 07601

Completed

Laura and Isaac Perlmutter Cancer Center ( Site 0034)

New York, New York, 10016

Completed

Sanford Fargo Medical Center ( Site 0039)

Fargo, North Dakota, 58102

Recruiting
Study Coordinator · Contact

Cleveland Clinic Main ( Site 0006)

Cleveland, Ohio, 44195

Completed

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0015)

Columbus, Ohio, 43210

Recruiting
Study Coordinator · Contact

Abramson Cancer Center of the University of Pennsylvania ( Site 0010)

Philadelphia, Pennsylvania, 19104

Recruiting
Study Coordinator · Contact

Sanford Cancer Center ( Site 0038)

Sioux Falls, South Dakota, 57104

Recruiting
Study Coordinator · Contact

The University of Texas MD Anderson Cancer Center ( Site 0009)

Houston, Texas, 77030

Recruiting
Study Coordinator · Contact