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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04165096
Collaborator
(none)
135
36
3
144.8
3.8
0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-5890 or MK-4830 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).

Enrollment in the pembrolizumab+MK-5890 arm has been completed with Amendment 4.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
135 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 21, 2020
Anticipated Primary Completion Date :
Feb 13, 2032
Anticipated Study Completion Date :
Feb 13, 2032

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab + MK-5890

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-5890 IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of MK-5890 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:
  • KEYTRUDA®
  • MK-3475
  • SCH 900475
  • Biological: MK-5890
    IV infusion

    Drug: diphenhydramine
    PO

    Drug: acetaminophen
    PO

    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:
  • KEYTRUDA®
  • MK-3475
  • SCH 900475
  • 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:
  • KEYTRUDA®
  • MK-3475
  • SCH 900475
  • Biological: MK-0482
    IV infusion

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [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.

    Secondary Outcome Measures

    1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [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.

    2. Number of Participants Who Experience One or More Adverse Events (AEs) [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.

    3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner MD Anderson Cancer Center ( Site 0001) Gilbert Arizona United States 85234
    2 City of Hope ( Site 0014) Duarte California United States 91010
    3 UCSF Medical Center at Mission Bay ( Site 0007) San Francisco California United States 94158
    4 Georgetown University ( Site 0036) Washington District of Columbia United States 20007
    5 University of Kentucky Markey Cancer Center ( Site 0019) Lexington Kentucky United States 40536-0293
    6 MedStar Franklin Square Medical Center ( Site 0033) Baltimore Maryland United States 21237
    7 Massachusetts General Hospital ( Site 0003) Boston Massachusetts United States 02114
    8 Dana Farber Cancer Institute ( Site 0002) Boston Massachusetts United States 02215
    9 Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031) Omaha Nebraska United States 68130
    10 Dartmouth Hitchcock Medical Center ( Site 0016) Lebanon New Hampshire United States 03766
    11 John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037) Hackensack New Jersey United States 07601
    12 Laura and Isaac Perlmutter Cancer Center ( Site 0034) New York New York United States 10016
    13 Cleveland Clinic ( Site 0006) Cleveland Ohio United States 44195
    14 Ohio State University Comprehensive Cancer Center ( Site 0015) Columbus Ohio United States 43210
    15 Abramson Cancer Center of the University of Pennsylvania ( Site 0010) Philadelphia Pennsylvania United States 19104
    16 The University of Texas MD Anderson Cancer Center ( Site 0009) Houston Texas United States 77030
    17 Petz Aladar Megyei Oktato Korhaz ( Site 0062) Gyor Gyor-Moson-Sopron Hungary 9024
    18 Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0061) Szolnok Jasz-Nagykun-Szolnok Hungary 5000
    19 Orszagos Koranyi Pulmonologiai Intezet ( Site 0060) Budapest Hungary 1121
    20 Soroka Medical Center ( Site 0072) Beer-Sheva Israel 8457108
    21 Rambam Health Care Campus-Oncology ( Site 0076) Haifa Israel 3109601
    22 Shaare Zedek Medical Center ( Site 0075) Jerusalem Israel 9103102
    23 Meir Medical Center ( Site 0071) Kfar-Saba Israel 4428164
    24 Rabin Medical Center ( Site 0074) Petah Tikva Israel 4941492
    25 Chaim Sheba Medical Center ( Site 0070) Ramat Gan Israel 5262000
    26 Sourasky Medical Center ( Site 0077) Tel Aviv Israel 6423906
    27 Azienda Ospedaliera Universitaria Careggi ( Site 0173) Florence Firenze Italy 50134
    28 Policlinico Gemelli di Roma ( Site 0174) Roma Lazio Italy 00168
    29 IRCCS Ospedale San Raffaele ( Site 0171) Milano Italy 20132
    30 Seoul National University Bundang Hospital ( Site 0081) Seongnam-si Kyonggi-do Korea, Republic of 13620
    31 Severance Hospital ( Site 0080) Seoul Korea, Republic of 03722
    32 Samsung Medical Center ( Site 0082) Seoul Korea, Republic of 06351
    33 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier Warszawa Mazowieckie Poland 02-781
    34 Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152) Koszalin Zachodniopomorskie Poland 75-581
    35 ICO L Hospitalet ( Site 0090) Hospitalet de Llobregat Barcelona Spain 08907
    36 Hospital Universitario Quiron Madrid ( Site 0091) Pozuelo de Alarcon Madrid Spain 28223

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT04165096
    Other Study ID Numbers:
    • 3475-01C
    • MK-3475-01C
    • KEYMAKER-U01C
    • 2020-001629-29
    First Posted:
    Nov 15, 2019
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 1, 2022