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)

Last updated: April 15, 2026
Sponsor: Merck Sharp & Dohme LLC
Overall Status: Active - Recruiting

Phase

N/A

Condition

N/A

Treatment

Tumor Imaging

Blood Sample Collection

Tumor Tissue Collection

Clinical Study ID

NCT04165798
3475-U01
MK-3475-U01
KEYMAKER-U01
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

  • Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous ornonsquamous NSCLC

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

Exclusion

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 2years

  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

  • Has an active infection requiring systemic therapy

Study Design

Total Participants: 1065
Treatment Group(s): 3
Primary Treatment: Tumor Imaging
Phase:
Study Start date:
December 19, 2019
Estimated Completion Date:
February 13, 2032

Study 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

Connect with a study center

  • Petz Aladar Megyei Oktato Korhaz ( Site 0062)

    Gyor, Gyor-Moson-Sopron 9024
    Hungary

    Site Not Available

  • Petz Aladar Megyei Oktato Korhaz ( Site 0062)

    Győr, Győr-Moson-Sopron 9024
    Hungary

    Completed

  • Petz Aladar Megyei Oktato Korhaz ( Site 0062)

    Győr 3052009, Győr-Moson-Sopron 3051977 9024
    Hungary

    Site Not Available

  • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0061)

    Szolnok, Jasz-Nagykun-Szolnok 5000
    Hungary

    Active - Recruiting

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

    Szolnok, Jász-Nagykun-Szolnok 5004
    Hungary

    Completed

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

    Szolnok 715126, Jász-Nagykun-Szolnok 719637 5004
    Hungary

    Site Not Available

  • Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)

    Budapest, 1121
    Hungary

    Completed

  • Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)

    Budapest 3054643, 1121
    Hungary

    Site Not Available

  • Soroka Medical Center ( Site 0072)

    Beer-Sheva, 8457108
    Israel

    Site Not Available

  • Soroka Medical Center ( Site 0072)

    Beersheba, 8457108
    Israel

    Completed

  • Soroka Medical Center ( Site 0072)

    Beersheba 295530, 8457108
    Israel

    Site Not Available

  • Rambam Health Care Campus-Oncology ( Site 0076)

    Haifa, 3109601
    Israel

    Completed

  • Rambam Health Care Campus-Oncology ( Site 0076)

    Haifa 294801, 3109601
    Israel

    Site Not Available

  • Shaare Zedek Medical Center ( Site 0075)

    Jerusalem, 9103102
    Israel

    Active - Recruiting

  • Shaare Zedek Medical Center ( Site 0075)

    Jerusalem 281184, 9103102
    Israel

    Site Not Available

  • Meir Medical Center ( Site 0071)

    Kfar Saba, 4428132
    Israel

    Completed

  • Meir Medical Center ( Site 0071)

    Kfar Saba 294514, 4428132
    Israel

    Site Not Available

  • Meir Medical Center ( Site 0071)

    Kfar-Saba, 4428164
    Israel

    Site Not Available

  • Rabin Medical Center ( Site 0074)

    Petah Tikva, 4941492
    Israel

    Completed

  • Rabin Medical Center ( Site 0074)

    Petah Tikva 293918, 4941492
    Israel

    Site Not Available

  • Chaim Sheba Medical Center ( Site 0070)

    Ramat Gan, 5262000
    Israel

    Active - Recruiting

  • Chaim Sheba Medical Center ( Site 0070)

    Ramat Gan 293788, 5262000
    Israel

    Site Not Available

  • Sourasky Medical Center ( Site 0077)

    Tel Aviv, 6423906
    Israel

    Completed

  • Sourasky Medical Center ( Site 0077)

    Tel Aviv 293397, 6423906
    Israel

    Site Not Available

  • Sourasky Medical Center ( Site 0077)

    Tel-Aviv, 6423906
    Israel

    Site Not Available

  • Azienda Ospedaliera Universitaria Careggi ( Site 0173)

    Florence, Firenze 50134
    Italy

    Completed

  • Azienda Ospedaliera Universitaria Careggi ( Site 0173)

    Florence 3176959, Firenze 50134
    Italy

    Site Not Available

  • IRCCS Ospedale San Raffaele ( Site 0171)

    Milan, 20132
    Italy

    Completed

  • IRCCS Ospedale San Raffaele ( Site 0171)

    Milan 6951411, 20132
    Italy

    Site Not Available

  • IRCCS Ospedale San Raffaele ( Site 0171)

    Milano, 20132
    Italy

    Site Not Available

  • Policlinico Gemelli di Roma ( Site 0174)

    Roma, 00168
    Italy

    Completed

  • Policlinico Gemelli di Roma ( Site 0174)

    Roma 8957247, 00168
    Italy

    Site Not Available

  • Seoul National University Bundang Hospital ( Site 0081)

    Seongnam-si, Kyonggi-do 13605
    Korea, Republic of

    Site Not Available

  • Samsung Medical Center ( Site 0082)

    Seoul, 06351
    Korea, Republic of

    Site Not Available

  • Severance Hospital ( Site 0080)

    Seoul, 03722
    Korea, Republic of

    Active - Recruiting

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

    Warsaw, Masovian Voivodeship 02-781
    Poland

    Active - Recruiting

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

    Warsaw 756135, Masovian Voivodeship 858787 02-781
    Poland

    Site Not Available

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

    Warszawa, Mazowieckie 02-781
    Poland

    Active - Recruiting

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

    Warszawa, Mazowieckie 02-781
    Poland

    Site Not Available

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

    Gdansk, Pomeranian Voivodeship 80-952
    Poland

    Completed

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

    Gdansk 3099434, Pomeranian Voivodeship 3337496 80-952
    Poland

    Site Not Available

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

    Gdańsk, Pomorskie 80-952
    Poland

    Site Not Available

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

    Koszalin, West Pomeranian Voivodeship 75-581
    Poland

    Site Not Available

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

    Koszalin 3095049, West Pomeranian Voivodeship 3337499 75-581
    Poland

    Site Not Available

  • Seoul National University Bundang Hospital ( Site 0081)

    Seongnam-si, Kyonggi-do 13620
    South Korea

    Completed

  • Seoul National University Bundang Hospital ( Site 0081)

    Seongnam-si 1897000, Kyonggi-do 13620
    South Korea

    Site Not Available

  • Samsung Medical Center ( Site 0082)

    Seoul, 06351
    South Korea

    Completed

  • Severance Hospital ( Site 0080)

    Seoul, 03722
    South Korea

    Completed

  • Samsung Medical Center ( Site 0082)

    Seoul 1835848, 06351
    South Korea

    Completed

  • Severance Hospital ( Site 0080)

    Seoul 1835848, 03722
    South Korea

    Site Not Available

  • ICO L Hospitalet ( Site 0090)

    Hospitalet de Llobregat, Barcelona 08907
    Spain

    Site Not Available

  • ICO L Hospitalet ( Site 0090)

    L'Hospitalet de Llobregat, Barcelona 08907
    Spain

    Active - Recruiting

  • ICO L Hospitalet ( Site 0090)

    L'Hospitalet de Llobregat 3120619, Barcelona 08907
    Spain

    Site Not Available

  • Hospital Universitario Quiron Madrid ( Site 0091)

    Pozuelo de Alarcon, Madrid 28223
    Spain

    Site Not Available

  • Hospital Clínic de Barcelona ( Site 0092)

    Barcelona, 08008
    Spain

    Active - Recruiting

  • Hospital Clínic de Barcelona ( Site 0092)

    Barcelona 3128760, 08008
    Spain

    Site Not Available

  • Hospital Universitario Quiron Madrid ( Site 0091)

    Madrid, 28223
    Spain

    Active - Recruiting

  • Hospital Universitario Quiron Madrid ( Site 0091)

    Madrid 3117735, 28223
    Spain

    Site Not Available

  • Changhua Christian Hospital ( Site 0181)

    Changhua, 50006
    Taiwan

    Active - Recruiting

  • Changhua Christian Hospital ( Site 0181)

    Changhua 1993459, 50006
    Taiwan

    Site Not Available

  • Taipei Medical University Hospital ( Site 0180)

    Taipei, 110301
    Taiwan

    Active - Recruiting

  • Taipei Medical University Hospital ( Site 0180)

    Taipei 1668341, 110301
    Taiwan

    Site Not Available

  • Chang Gung Medical Foundation-Linkou Branch ( Site 0182)

    Taoyuan District, 33305
    Taiwan

    Active - Recruiting

  • Chang Gung Medical Foundation-Linkou Branch ( Site 0182)

    Taoyuan District 1667905, 33305
    Taiwan

    Site Not Available

  • COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0463)

    Cherkasy, Cherkasy Oblast 18009
    Ukraine

    Active - Recruiting

  • COMMUNAL NONPROFIT ENTERPRISE "CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0463)

    Cherkasy 710791, Cherkasy Oblast 710802 18009
    Ukraine

    Site Not Available

  • Communal Non-Commercial Enterprise "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Reg ( Site 0460)

    Ivano-Frankivsk, Ivano-Frankivsk Oblast 76018
    Ukraine

    Active - Recruiting

  • Communal Non-Commercial Enterprise "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Reg ( Site 0460)

    Ivano-Frankivsk 707471, Ivano-Frankivsk Oblast 707470 76018
    Ukraine

    Site Not Available

  • ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0461)

    Rivne, Rivne Oblast 33010
    Ukraine

    Active - Recruiting

  • ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0461)

    Rivne 695594, Rivne Oblast 695592 33010
    Ukraine

    Site Not Available

  • Uzhhorod Multispecialty City Clinical Hospital ( Site 0462)

    Uzhhorod, Zakarpattia Oblast 88000
    Ukraine

    Active - Recruiting

  • Uzhhorod Multispecialty City Clinical Hospital ( Site 0462)

    Uzhhorod 690548, Zakarpattia Oblast 687869 88000
    Ukraine

    Site Not Available

  • Banner MD Anderson Cancer Center ( Site 0001)

    Gilbert, Arizona 85234
    United States

    Completed

  • Banner MD Anderson Cancer Center ( Site 0001)

    Gilbert 5295903, Arizona 5551752 85234
    United States

    Site Not Available

  • City of Hope ( Site 0014)

    Duarte, California 91010
    United States

    Completed

  • UCSF Medical Center at Mission Bay ( Site 0007)

    San Francisco, California 94158
    United States

    Completed

  • City of Hope ( Site 0014)

    Duarte 5344147, California 5332921 91010
    United States

    Site Not Available

  • UCSF Medical Center at Mission Bay ( Site 0007)

    San Francisco 5391959, California 5332921 94158
    United States

    Site Not Available

  • Georgetown University ( Site 0036)

    Washington, District of Columbia 20007
    United States

    Site Not Available

  • Georgetown University ( Site 0036)

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

    Completed

  • Georgetown University ( Site 0036)

    Washington D.C. 4140963, District of Columbia 4138106 20007
    United States

    Site Not Available

  • University of Kentucky Markey Cancer Center ( Site 0019)

    Lexington, Kentucky 40536-0293
    United States

    Completed

  • University of Kentucky Markey Cancer Center ( Site 0019)

    Lexington 4297983, Kentucky 6254925 40536-0293
    United States

    Site Not Available

  • MedStar Franklin Square Medical Center ( Site 0033)

    Baltimore, Maryland 21237
    United States

    Completed

  • MedStar Franklin Square Medical Center ( Site 0033)

    Baltimore 4347778, Maryland 4361885 21237
    United States

    Site Not Available

  • Dana Farber Cancer Institute ( Site 0002)

    Boston, Massachusetts 02215
    United States

    Completed

  • Massachusetts General Hospital ( Site 0003)

    Boston, Massachusetts 02114
    United States

    Completed

  • Dana Farber Cancer Institute ( Site 0002)

    Boston 4930956, Massachusetts 6254926 02215
    United States

    Site Not Available

  • Massachusetts General Hospital ( Site 0003)

    Boston 4930956, Massachusetts 6254926 02114
    United States

    Site Not Available

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

    Omaha, Nebraska 68130
    United States

    Completed

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

    Omaha 5074472, Nebraska 5073708 68130
    United States

    Site Not Available

  • Dartmouth Hitchcock Medical Center ( Site 0016)

    Lebanon, New Hampshire 03766
    United States

    Active - Recruiting

  • Dartmouth Hitchcock Medical Center ( Site 0016)

    Lebanon 5088597, New Hampshire 5090174 03766
    United States

    Site Not Available

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

    Hackensack, New Jersey 07601
    United States

    Completed

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

    Hackensack 5098706, New Jersey 5101760 07601
    United States

    Site Not Available

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

    New York, New York 10016
    United States

    Completed

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

    New York 5128581, New York 5128638 10016
    United States

    Site Not Available

  • Sanford Fargo Medical Center ( Site 0039)

    Fargo, North Dakota 58102
    United States

    Active - Recruiting

  • Sanford Fargo Medical Center ( Site 0039)

    Fargo 5059163, North Dakota 5690763 58102
    United States

    Site Not Available

  • Cleveland Clinic ( Site 0006)

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • Cleveland Clinic Main ( Site 0006)

    Cleveland, Ohio 44195
    United States

    Completed

  • Ohio State University Comprehensive Cancer Center ( Site 0015)

    Columbus, Ohio 43210
    United States

    Active - Recruiting

  • Cleveland Clinic Main ( Site 0006)

    Cleveland 5150529, Ohio 5165418 44195
    United States

    Site Not Available

  • Ohio State University Comprehensive Cancer Center ( Site 0015)

    Columbus 4509177, Ohio 5165418 43210
    United States

    Site Not Available

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

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

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

    Philadelphia 4560349, Pennsylvania 6254927 19104
    United States

    Site Not Available

  • Sanford Cancer Center ( Site 0038)

    Sioux Falls, South Dakota 57104
    United States

    Active - Recruiting

  • Sanford Cancer Center ( Site 0038)

    Sioux Falls 5231851, South Dakota 5769223 57104
    United States

    Site Not Available

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

    Houston, Texas 77030
    United States

    Active - Recruiting

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

    Houston 4699066, Texas 4736286 77030
    United States

    Site Not Available

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