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)

Recruiting now · Phase 1/Phase 2

Conditions studied: Carcinoma, Non-Small-Cell Lung

In brief

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).

Key facts

Study ID: NCT04165070
Run by: Merck Sharp & Dohme LLC
People needed: 450
Starts: 2019-12-19
Expected to finish: 2032-10-13
Last updated by the study team: 2026-07-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site 0460) — Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine (enrolling)
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0015) — Columbus, Ohio, United States (enrolling)
Abramson Cancer Center of the University of Pennsylvania ( Site 0010) — Philadelphia, Pennsylvania, United States (enrolling)
Sanford Cancer Center ( Site 0038) — Sioux Falls, South Dakota, United States (enrolling)
The University of Texas MD Anderson Cancer Center ( Site 0009) — Houston, Texas, United States (enrolling)
ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0461) — Rivne, Rivne Oblast, Ukraine (enrolling)
Uzhhorod Multispecialty City Clinical Hospital ( Site 0462) — Uzhhorod, Zakarpattia Oblast, Ukraine (enrolling)
Changhua Christian Hospital ( Site 0181) — Changhua, Taiwan (enrolling)
Taipei Medical University Hospital ( Site 0180) — Taipei, Taiwan (enrolling)
Dartmouth Hitchcock Medical Center ( Site 0016) — Lebanon, New Hampshire, United States (enrolling)
Shaare Zedek Medical Center ( Site 0075) — Jerusalem, Israel (enrolling)
Chang Gung Medical Foundation-Linkou Branch ( Site 0182) — Taoyuan, Taiwan (enrolling)
COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0463) — Cherkasy, Cherkasy Oblast, Ukraine (enrolling)
Chaim Sheba Medical Center ( Site 0070) — Ramat Gan, Israel (enrolling)
Sanford Fargo Medical Center ( Site 0039) — Fargo, North Dakota, United States (enrolling)
University of Kentucky Markey Cancer Center ( Site 0019) — Lexington, Kentucky, United States
MedStar Franklin Square Medical Center ( Site 0033) — Baltimore, Maryland, United States
Massachusetts General Hospital ( Site 0003) — Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0002) — Boston, Massachusetts, United States
Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031) — Omaha, Nebraska, United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037) — Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0034) — New York, New York, United States
Cleveland Clinic Main ( Site 0006) — Cleveland, Ohio, United States
Petz Aladar Megyei Oktato Korhaz ( Site 0062) — Győr, Győr-Moson-Sopron, Hungary
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061) — Szolnok, Jász-Nagykun-Szolnok, Hungary

Full record on ClinicalTrials.gov

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