KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

May 21, 2026 updated by: Merck Sharp & Dohme LLC

KEYMAKER-U01 Master Study: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents, Pembrolizumab, and Chemotherapy, Alone or in Combination, in Participants With Non-small Cell Lung Cancer (NSCLC)

This study is referred to as the "umbrella master protocol" for pembrolizumab (MK-3475) in the treatment of non-small cell lung cancer (NSCLC). This pembrolizumab NSCLC umbrella master protocol uses a platform design and consists of this master screening study and additional substudies. Each substudy will enroll a different population of NSCLC participants.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The following pembrolizumab substudies will evaluate the efficacy of different investigational agents in combination with pembrolizumab given in sequence or in combination with pembrolizumab PLUS chemotherapy:

  • 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) (MK-3475-01A) - NCT04165070
  • KEYMAKER-U01 Substudy 2: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Treatment Naïve Patients with PD-L1 Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B) - NCT04165083
  • KEYMAKER-U01 Substudy 3: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents in Combination with Pembrolizumab in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Previously Treated with anti-PD-(L)1 Therapy (MK-3475-01C) - NCT04165096
  • KEYMAKER-U01 Substudy 01E: A Phase 2 Umbrella Study With Rolling Arms of Investigational Agents With or Without Chemotherapy in Combination With Pembrolizumab in Treatment of Participants With Newly Diagnosed Resectable Stages II-IIIB (N2) Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E) - NCT06788912
  • KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Second-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations (MK-3475-01F) - NCT number pending
  • KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01G) - NCT06731907
  • KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants with Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H) - NCT06780085
  • KEYMAKER-U01 Substudy 01I: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I) - NCT06780098
  • KEYMAKER-U01 Substudy 01J: A Randomized Phase 2 Umbrella Study With Rolling Arms of Investigational Agents for First-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations (MK-3475-01J) - NCT number pending

Study Type

Observational

Enrollment (Estimated)

1065

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: +972587040620
      • 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
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier ( Site 0151)
        • Contact:
          • Study Coordinator
          • Phone Number: +48225463066
    • 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
      • Barcelona, Spain, 08008
        • Recruiting
        • Hospital Clinic de Barcelona ( Site 0092)
        • Contact:
          • Study Coordinator
          • Phone Number: 34 932275402
      • Madrid, Spain, 28223
        • Recruiting
        • Hospital Universitario Quiron Madrid ( Site 0091)
        • Contact:
          • Study Coordinator
          • Phone Number: +34914521987
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Recruiting
        • ICO L Hospitalet ( Site 0090)
        • Contact:
          • Study Coordinator
          • Phone Number: 0034932607744
  • Taiwan
      • Changhua, Taiwan, 50006
        • Recruiting
        • Changhua Christian Hospital ( Site 0181)
        • Contact:
          • Study Coordinator
          • Phone Number: +88647238595
      • 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 Oncological Center" of Ivano-Frankivsk Reg ( 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
        • Completed
        • 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 at NYU Langone Health ( 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
        • Ohio State University Comprehensive Cancer Center ( 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

Sampling Method

Probability Sample

Study Population

Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC

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
  • Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1

Exclusion Criteria:

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

  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection requiring systemic therapy

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Prospective NSCLC Participants
Male and female participants with histologically-confirmed diagnosis of squamous or nonsquamous NSCLC will be screened for participation in 1 of several pembrolizumab substudies.
Diagnostic test: Tumor Imaging
Participants will undergo tumor imaging using either a magnetic resonance imaging (MRI) scan or a computed tomography (CT) scan.
Procedure: Tumor Tissue Collection
Participants without archival tumor tissue samples will undergo tumor tissue collection for newly obtained tumor tissue.
Procedure: Blood Sample Collection

Participants will have blood samples drawn for analysis of:

  • genetics
  • ribonucleic acid (RNA)
  • serum biomarker
  • plasma biomarker
  • circulating tumor DNA (ctDNA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) <1% vs. TPS =1%
Time Frame: Up to approximately 1 month
Participants' tumors will be evaluated for their PD-L1 tumor expression level using archival tumor tissue samples or newly obtained tumor tissue. The percentage of participants who have a Tumor Proportion Score (TPS) <1% vs. a TPS =1% will be presented.
Up to approximately 1 month
Tumor Histology Status: Squamous Non-small Cell Lung Cancer (NSCLC) vs. Nonsquamous NSCLC
Time Frame: Up to approximately 1 month
Participants' tumors will be evaluated for their tumor histology status as being either squamous vs. nonsquamous NSCLC using archival or newly obtained tumor tissue samples. The percentage of participants who have squamous vs. nonsquamous NSCLC will be presented.
Up to approximately 1 month

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 13, 2019

First Submitted That Met QC Criteria

November 13, 2019

First Posted (Actual)

November 18, 2019

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 21, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-U01
  • MK-3475-U01 (Other Identifier: MSD)
  • KEYMAKER-U01 (Other Identifier: MSD)

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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