The purpose of this study is to determine the safety, tolerability, and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy or immunotherapy in participants with unresectable or metastatic non-small cell lung cancer (NSCLC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
267
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)
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: At least a 30% decrease in the sum of diameters of target lesions) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).
Time frame: Up to approximately 2 years
Part 2 Cohorts D4 and H: Objective Response Rate (ORR)
For participants who demonstrated a confirmed response (Complete Response \[CR\]: Disappearance of all target lesions or Partial Response \[PR\]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR.
Time frame: Up to approximately 2 years
All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days; Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting \>3 days despite optimal supportive care; Any Grade 3 or Grade 4 non-hematologic laboratory value requiring treatment or hospitalization, or persisting for \>1 week; Febrile neutropenia Grade 3 or Grade 4; Qualifying thrombocytopenia \<25,000/mm\^3; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Missing \>10% of erlotinib or gefitinib doses as a result of adverse events (AEs) during the DLT window of observation; or Grade 5 toxicity.
Time frame: Cycle 1 (Up to 21 days)
Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 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 at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was assessed by BICR.
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IV on Day 1 of each 3-week cycle
IV on Day 1 of each 3-week cycle
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
Orally tablet once daily
Oral tablet once daily
Time frame: Up to approximately 2 years
Part 2 Cohorts G+ and G-: Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 2 years
Part 2 Cohorts G+ and G-: Duration of Response (DOR)
For participants who demonstrated a confirmed response (Complete Response \[CR\]: Disappearance of all target lesions or Partial Response \[PR\]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR.
Time frame: Up to approximately 2 years