KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B)

NCT04165083 | Completed Phase 2 FDA Drug

• 6 other identifiers: 3475-01BMK-3475-01BKEYMAKER-U01B2023-506933-32-00U1111-1294-65182020-001627-14
• Study Type: interventional
• Target: 102
• Locations: 7 countries
• Sites: 39

Brief Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC that is PD-L1 positive. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01). The pembrolizumab+ MK-0482 arm was added with Amendment 6.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Programmed Cell Death Receptor 1 (PD-1, PD1); Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1); Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to approximately 24 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 24 months

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

  Up to approximately 27 months

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

  Up to approximately 24 months

Study Arms (2)

Pembrolizumab + MK-4830

EXPERIMENTAL

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years)

Biological: Pembrolizumab; Biological: MK-4830

Pembrolizumab + MK-0482

EXPERIMENTAL

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years)

Biological: Pembrolizumab; Biological: MK-0482

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475, SCH 900475

Pembrolizumab + MK-0482; Pembrolizumab + MK-4830

MK-4830 BIOLOGICAL

IV infusion

Pembrolizumab + MK-4830

MK-0482 BIOLOGICAL

IV infusion

Pembrolizumab + MK-0482

Eligibility Criteria

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

You may qualify if:

• Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous or non-squamous NSCLC
• Has non-squamous NSCLC and is 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 metastatic NSCLC
• Has programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%
• Is able to complete all screening procedures within the 35-day screening window.
• Male participants must agree to use contraception and refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study treatment
• Female participants must not be pregnant or breastfeeding, and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to use contraception during the treatment period and for at least 120 days after the last dose of study treatment
• Has adequate organ function within 10 days of initiation of study treatment

You may not qualify if:

• 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, or New York Heart Association Class III or IV congestive heart failure
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
• Has had major surgery \<3 weeks before the first dose of study treatment
• 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 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (39)

Banner MD Anderson Cancer Center ( Site 0001)

Gilbert, Arizona, 85234, United States

Location

City of Hope ( Site 0014)

Duarte, California, 91010, United States

Location

UCSF Medical Center at Mission Bay ( Site 0007)

San Francisco, California, 94158, United States

Location

Georgetown University ( Site 0036)

Washington D.C., District of Columbia, 20007, United States

Location

University of Kentucky Markey Cancer Center ( Site 0019)

Lexington, Kentucky, 40536-0293, United States

Location

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237, United States

Location

Massachusetts General Hospital ( Site 0003)

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute ( Site 0002)

Boston, Massachusetts, 02215, United States

Location

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

Omaha, Nebraska, 68130, United States

Location

Dartmouth Hitchcock Medical Center ( Site 0016)

Lebanon, New Hampshire, 03766, United States

Location

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

Hackensack, New Jersey, 07601, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0034)

New York, New York, 10016, United States

Location

Sanford Fargo Medical Center ( Site 0039)

Fargo, North Dakota, 58102, United States

Location

Cleveland Clinic Main ( Site 0006)

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center ( Site 0015)

Columbus, Ohio, 43210, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

Sanford Cancer Center ( Site 0038)

Sioux Falls, South Dakota, 57104, United States

Location

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

Houston, Texas, 77030, United States

Location

Petz Aladar Megyei Oktato Korhaz ( Site 0062)

Győr, Győr-Moson-Sopron, 9024, Hungary

Location

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)

Szolnok, Jász-Nagykun-Szolnok, 5004, Hungary

Location

Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)

Budapest, 1121, Hungary

Location

Soroka Medical Center ( Site 0072)

Beersheba, 8457108, Israel

Location

Rambam Health Care Campus-Oncology ( Site 0076)

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center ( Site 0075)

Jerusalem, 9103102, Israel

Location

Meir Medical Center ( Site 0071)

Kfar Saba, 4428132, Israel

Location

Rabin Medical Center ( Site 0074)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 0070)

Ramat Gan, 5262000, Israel

Location

Sourasky Medical Center ( Site 0077)

Tel Aviv, 6423906, Israel

Location

Azienda Ospedaliera Universitaria Careggi ( Site 0173)

Florence, Firenze, 50134, Italy

Location

IRCCS Ospedale San Raffaele ( Site 0171)

Milan, 20132, Italy

Location

Policlinico Gemelli di Roma ( Site 0174)

Roma, 00168, Italy

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 0151)

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Seoul National University Bundang Hospital ( Site 0081)

Seongnam-si, Kyonggi-do, 13620, South Korea

Location

Severance Hospital ( Site 0080)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 0082)

Seoul, 06351, South Korea

Location

ICO L Hospitalet ( Site 0090)

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Quiron Madrid ( Site 0091)

Madrid, 28223, Spain

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: November 15, 2019
• Study Start: December 19, 2019
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (18); PL (3); IL (7); KR (3); HU (3); IT (3); ES (2)