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Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYNOTE-01A)

NCT04165070

Description:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-7684 in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYNOTE-01A)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 3475-01A
  • SECONDARY ID: MK-3475-01A
  • SECONDARY ID: KEYNOTE-01A
  • SECONDARY ID: 2020-001626-56
  • NCT ID: NCT04165070

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, SCH 900475, KEYTRUDA®Pembrolizumab + MK-7684 + Carboplatin + Paclitaxel
CarboplatinPARAPLATIN®Pembrolizumab + MK-7684 + Carboplatin + Paclitaxel
PaclitaxelABRAXANE®Pembrolizumab + MK-7684 + Carboplatin + Paclitaxel
PemetrexedALIMTA®Pembrolizumab + MK-7684 + Pemetrexed
MK-7684Pembrolizumab + MK-7684 + Carboplatin + Paclitaxel

Purpose

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with MK-7684 in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01).

Detailed Description

      The Master screening protocol is MK-3475-U01 - NCT04165798
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + MK-7684 + Carboplatin + PaclitaxelExperimentalOn Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS MK-7684 IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-7684 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
  • Pembrolizumab
  • Carboplatin
  • Paclitaxel
  • MK-7684
Pembrolizumab + MK-7684 + PemetrexedExperimentalOn Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-7684 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-7684 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
  • Pembrolizumab
  • Carboplatin
  • Pemetrexed
  • MK-7684

Eligibility Criteria

        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 provide archival tumor tissue sample or newly obtained core or excisional
             biopsy of a tumor lesion not previously irradiated

          -  Has not received prior systemic treatment for their metastatic NSCLC

          -  Is able to complete all screening procedures within the 28-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 for at least 120 days after the last dose of
             pembrolizumab and for at least 180 days after the last dose of chemotherapy

          -  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 pembrolizumab and for at least 180 days
                  after the last dose of 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 prior to 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 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 prior to first dose of study treatment

          -  Is expected to require any other form of antineoplastic therapy while on study

          -  Has symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®, Eli
             Lilly)

          -  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 pre-existing neuropathy that is moderate in intensity

          -  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

          -  Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4
             (CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration
             of the study

          -  Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be
             discontinued for the duration of the study

          -  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

          -  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 prior to 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)

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to 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
      
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 to the first 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 Discontinue 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-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

June 12, 2020