KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C)

NCT04165096 | Completed Phase 2 FDA Drug

• 6 other identifiers: 3475-01CMK-3475-01CKEYMAKER-U01C2023-506934-56-00U1111-1294-65892020-001629-29
• Study Type: interventional
• Target: 128
• 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 boserolimab (MK-5890), MK-4830, MK-0482 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

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 (3)

Boserolimab + Pembrolizumab

EXPERIMENTAL

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).

Biological: Pembrolizumab; Biological: Boserolimab; Drug: diphenhydramine; Drug: acetaminophen

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

Boserolimab + Pembrolizumab; Pembrolizumab + MK-0482; Pembrolizumab + MK-4830

Boserolimab BIOLOGICAL

IV infusion

Also known as: MK-5890

Boserolimab + Pembrolizumab

MK-4830 BIOLOGICAL

IV infusion

Pembrolizumab + MK-4830

diphenhydramine DRUG

PO

Boserolimab + Pembrolizumab

acetaminophen DRUG

PO

Boserolimab + Pembrolizumab

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
• Have progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
• Have progressive disease (PD) during/after platinum doublet chemotherapy
• 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 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)

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 ( 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, 5000, 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

Policlinico Gemelli di Roma ( Site 0174)

Rome, Lazio, 00168, Italy

Location

IRCCS Ospedale San Raffaele ( Site 0171)

Milan, 20132, Italy

Location

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

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)

Pozuelo de Alarcón, 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; Diphenhydramine; Acetaminophen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Acetanilides; Anilides; Amides; Aniline Compounds

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: 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: January 21, 2020
• Primary Completion: April 30, 2025
• Study Completion: May 28, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

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