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KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC ) (MK-3475-01B/KEYMAKER-U01B)

NCT04165083

Description:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC that is PD-L1 positive. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC ) (MK-3475-01B/KEYMAKER-U01B)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 3475-01B
  • SECONDARY ID: MK-3475-01B
  • SECONDARY ID: KEYMAKER-U01B
  • SECONDARY ID: 2020-001627-14
  • NCT ID: NCT04165083

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®, MK-3475, SCH 900475Pembrolizumab + MK-4830
MK-4830Pembrolizumab + MK-4830

Purpose

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC that is PD-L1 positive. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Detailed Description

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

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + MK-4830ExperimentalOn 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)
  • Pembrolizumab
  • MK-4830

Eligibility Criteria

        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

          -  Has not received prior systemic treatment for metastatic NSCLC

          -  Has programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

          -  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 (non-infectious) 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 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)

          -  Has received a live vaccine within 30 days before the first dose of study treatment

          -  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 receptor 1 (PD-1),
             anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death
             receptor ligand 2 (PD-L2) agent or prior therapy targeting other immuno-regulatory
             receptors or mechanisms

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description: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.
Measure:Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame:Up to approximately 27 months
Safety Issue:
Description: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.
Measure:Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame:Up to approximately 24 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death Receptor 1 (PD-1, PD1)
  • Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1)
  • Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)

Last Updated

April 19, 2021