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

December 7, 2023 updated by: Merck Sharp & Dohme LLC

KEYMAKER-U01 Master Study: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents With Either Pembrolizumab in Combination With Chemotherapy or With Pembrolizumab Alone in Patients With Advanced 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 three substudies. Each substudy will enroll a different population of NSCLC participants.

The goal of this umbrella master protocol is to screen potential participants with NSCLC for enrollment into 1 of 3 substudies. Participants must first enroll in this pembrolizumab master protocol study and undergo screening for NSCLC that will be used to assign them to participation in 1 of 3 pembrolizumab substudies.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The following 3 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 1: A Phase 2, Umbrella Study with Rolling Arms of Investigational Agents with Pembrolizumab in Combination with Chemotherapy in Treatment-Naïve Patients with Advanced 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

Study Type

Observational

Enrollment (Estimated)

260

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
        • Recruiting
        • Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
        • Contact:
          • Study Coordinator
          • Phone Number: +3613913364
    • Gyor-Moson-Sopron
      • Gyor, Gyor-Moson-Sopron, Hungary, 9024
        • Recruiting
        • Petz Aladar Megyei Oktato Korhaz ( Site 0062)
        • Contact:
          • Study Coordinator
          • Phone Number: +3696418244
    • Jasz-Nagykun-Szolnok
      • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
        • Recruiting
        • Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
        • Contact:
          • Study Coordinator
          • Phone Number: +36209323256
  • Israel
      • Beer-Sheva, Israel, 8457108
        • Completed
        • Soroka Medical Center ( Site 0072)
      • Haifa, Israel, 3109601
        • Recruiting
        • Rambam Health Care Campus-Oncology ( Site 0076)
        • Contact:
          • Study Coordinator
          • Phone Number: 972-4-7776735
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center ( Site 0075)
        • Contact:
          • Study Coordinator
          • Phone Number: +972587040620
      • Kfar-Saba, Israel, 4428132
        • Recruiting
        • Meir Medical Center ( Site 0071)
        • Contact:
          • Study Coordinator
          • Phone Number: +97297472414
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center ( Site 0074)
        • Contact:
          • Study Coordinator
          • Phone Number: +97239378101
      • Ramat Gan, Israel, 5262000
        • Recruiting
        • Chaim Sheba Medical Center ( Site 0070)
        • Contact:
          • Study Coordinator
          • Phone Number: +97235307096
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Sourasky Medical Center ( Site 0077)
        • Contact:
          • Study Coordinator
          • Phone Number: +972-3-6973082
  • Italy
      • Milano, Italy, 20132
        • Recruiting
        • IRCCS Ospedale San Raffaele ( Site 0171)
        • Contact:
          • Study Coordinator
          • Phone Number: +390226436627
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi ( Site 0173)
        • Contact:
          • Study Coordinator
          • Phone Number: +393209225506
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Recruiting
        • Policlinico Gemelli di Roma ( Site 0174)
        • Contact:
          • Study Coordinator
          • Phone Number: +390630155202
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital ( Site 0080)
        • Contact:
          • Study Coordinator
          • Phone Number: 82022281004
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center ( Site 0082)
        • Contact:
          • Study Coordinator
          • Phone Number: +82215993114
    • Kyonggi-do
      • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
        • Recruiting
        • Seoul National University Bundang Hospital ( Site 0081)
        • Contact:
          • Study Coordinator
          • Phone Number: +82215883369
  • Poland
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 02-781
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
        • Contact:
          • Study Coordinator
          • Phone Number: +48225463066
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-952
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
        • Contact:
          • Study Coordinator
          • Phone Number: +48583492979
    • Zachodniopomorskie
      • Koszalin, Zachodniopomorskie, Poland, 75-581
        • Active, not recruiting
        • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
  • Spain
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Recruiting
        • ICO L Hospitalet ( Site 0090)
        • Contact:
          • Study Coordinator
          • Phone Number: +34605431976
    • Madrid
      • Pozuelo de Alarcon, Madrid, Spain, 28223
        • Recruiting
        • Hospital Universitario Quiron Madrid ( Site 0091)
        • Contact:
          • Study Coordinator
          • Phone Number: +34914521987
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Recruiting
        • Banner MD Anderson Cancer Center ( Site 0001)
        • Contact:
          • Study Coordinator
          • Phone Number: 480-256-3425
    • 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, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University ( Site 0036)
        • Contact:
          • Study Coordinator
          • Phone Number: 202-444-2223
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0293
        • Recruiting
        • University of Kentucky Markey Cancer Center ( Site 0019)
        • Contact:
          • Study Coordinator
          • Phone Number: 859-218-0131
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Recruiting
        • MedStar Franklin Square Medical Center ( Site 0033)
        • Contact:
          • Study Coordinator
          • Phone Number: 443-777-7364
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital ( Site 0003)
        • Contact:
          • Study Coordinator
          • Phone Number: 617-724-4000
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute ( Site 0002)
        • Contact:
          • Study Coordinator
          • Phone Number: 617-632-4767
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
        • Contact:
          • Study Coordinator
          • Phone Number: 402-691-6971
    • 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
        • Recruiting
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0034)
        • Contact:
          • Study Coordinator
          • Phone Number: 929-455-2428
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Recruiting
        • Sanford Fargo Medical Center ( Site 0039)
        • Contact:
          • Study Coordinator
          • Phone Number: 701-234-2358
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic ( Site 0006)
        • Contact:
          • Study Coordinator
          • Phone Number: 216-636-6888
      • 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:

  • 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 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
  • Has adequate organ function within 10 days of initiation of study treatment
  • Male participants must agree to use contraception and should refrain from donating sperm during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
  • Substudies 2 and 3: for at least 120 days after study treatments

  • Female participants must not be pregnant or breastfeeding, and at least 1 of the following conditions apply:

    1. Not a woman of childbearing potential (WOCBP), OR
    2. A WOCBP who agrees to use contraception during the treatment period and:
  • Substudy 1: for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy.

  • Substudies 2 and 3: for at least 120 days after study treatment

    *Substudies 1 and 2 Only:

  • Has not received prior systemic treatment for their metastatic NSCLC

    *Substudy 2 Only:

  • Has a programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

    *Substudy 3 Only:

  • Has 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
  • Has progressive disease during/after platinum doublet chemotherapy

Exclusion Criteria:

  • 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/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • 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 HIV infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • 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 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
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment

  • Has had an allogenic tissue/solid organ transplant

    *Substudy 1 Only:

  • Has symptomatic ascites or pleural effusion (if receiving pemetrexed)
  • 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
  • Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period (8-day period for long acting agents such as peroxicam), for participants who will receive pemetrexed
  • 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

    *Substudies 1 and 2 Only:

  • Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease

  • Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy targeting other immunoregulatory receptors or mechanisms

    *Substudy 3 Only:

  • Has received prior therapy targeting other immuno-regulatory receptors or mechanisms, not including anti-PD-(L)1 agents
  • Has participated in Substudies 1 or 2

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 3 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

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)

December 8, 2023

Last Update Submitted That Met QC Criteria

December 7, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

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

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/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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