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)

February 9, 2024 updated by: Merck Sharp & Dohme LLC

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Study Type

Interventional

Enrollment (Estimated)

135

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hungary
      • Budapest, Hungary, 1121
        • Orszagos Koranyi Pulmonologiai Intezet ( Site 0060)
    • Gyor-Moson-Sopron
      • Gyor, Gyor-Moson-Sopron, Hungary, 9024
        • Petz Aladar Megyei Oktato Korhaz ( Site 0062)
    • Jasz-Nagykun-Szolnok
      • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
        • Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0061)
  • Israel
      • Beer-Sheva, Israel, 8457108
        • Soroka Medical Center ( Site 0072)
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus-Oncology ( Site 0076)
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center ( Site 0075)
      • Kfar-Saba, Israel, 4428132
        • Meir Medical Center ( Site 0071)
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center ( Site 0074)
      • Ramat Gan, Israel, 5262000
        • Chaim Sheba Medical Center ( Site 0070)
      • Tel Aviv, Israel, 64239
        • Sourasky Medical Center ( Site 0077)
  • Italy
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele ( Site 0171)
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Azienda Ospedaliera Universitaria Careggi ( Site 0173)
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Policlinico Gemelli di Roma ( Site 0174)
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital ( Site 0080)
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center ( Site 0082)
    • Kyonggi-do
      • Seongnam-si, Kyonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital ( Site 0081)
  • Poland
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
    • Zachodniopomorskie
      • Koszalin, Zachodniopomorskie, Poland, 75-581
        • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
  • Spain
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
        • ICO L Hospitalet ( Site 0090)
    • Madrid
      • Pozuelo de Alarcon, Madrid, Spain, 28223
        • Hospital Universitario Quiron Madrid ( Site 0091)
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center ( Site 0001)
    • California
      • Duarte, California, United States, 91010
        • City of Hope ( Site 0014)
      • San Francisco, California, United States, 94158
        • UCSF Medical Center at Mission Bay ( Site 0007)
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University ( Site 0036)
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0293
        • University of Kentucky Markey Cancer Center ( Site 0019)
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • MedStar Franklin Square Medical Center ( Site 0033)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ( Site 0003)
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute ( Site 0002)
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03766
        • Dartmouth Hitchcock Medical Center ( Site 0016)
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center ( Site 0034)
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Sanford Fargo Medical Center ( Site 0039)
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic ( Site 0006)
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center ( Site 0015)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center ( Site 0038)
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center ( Site 0009)

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

Description

Inclusion:

  • 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:

    1. Not a woman of childbearing potential (WOCBP) OR
    2. 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

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 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)
  • 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
  • Has participated in Substudies 1 or 2
  • Has 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

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab + MK-4830
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
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Biological: MK-4830
IV infusion
Experimental: Pembrolizumab + MK-0482
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
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Biological: MK-0482
IV infusion
Experimental: Boserolimab + Pembrolizumab
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
IV infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: diphenhydramine
PO
Drug: acetaminophen
PO
Biological: Boserolimab
IV infusion
Other Names:
  • MK-5890

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 24 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 24 months
PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Up to approximately 24 months
Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame: Up to approximately 27 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Up to approximately 27 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to approximately 24 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Up to approximately 24 months

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)

January 21, 2020

Primary Completion (Estimated)

February 13, 2032

Study Completion (Estimated)

February 13, 2032

Study Registration Dates

First Submitted

November 14, 2019

First Submitted That Met QC Criteria

November 14, 2019

First Posted (Actual)

November 15, 2019

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-01C
  • MK-3475-01C (Other Identifier: Merck)
  • KEYMAKER-U01C (Other Identifier: Merck)
  • 2020-001629-29 (EudraCT Number)

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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