The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib \[TAGRISSO®\] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS. Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
492
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Cedars-Sinai Medical Center ( Site 0070)
Los Angeles, California, United States
Pacific Cancer Care ( Site 0058)
Monterey, California, United States
UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0092)
Orange, California, United States
St. Joseph Heritage Healthcare ( Site 0003)
Santa Rosa, California, United States
North Shore University Health System ( Site 0030)
Evanston, Illinois, United States
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is 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. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~40 months
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~51 months
Objective Response Rate (ORR) Per RECIST 1.1
ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience 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, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.
Time frame: Up to ~51 months
Duration of Response (DOR) Per RECIST 1.1
DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~51 months
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented.
Time frame: Baseline and Week 18
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea
TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough \[EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?\], chest pain \[EORTC QLQ-LC13 Item 10; Have you had pain in your chest?\], or dyspnea \[EORTC QLQ-C30 Item 8; Were you short of breath?\]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented.
Time frame: Baseline and up to ~51 months
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.
Time frame: Up to ~44 months
Percentage of Participants Who Discontinued Study Treatment Due to AEs
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.
Time frame: Up to ~41 months
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Siouxland Regioinal Cancer Center dba June E. Nylen Cancer Center ( Site 0065)
Sioux City, Iowa, United States
Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 0048)
Edina, Minnesota, United States
Saint Lukes Hospital of Kansas City ( Site 0060)
Kansas City, Missouri, United States
New York Oncology Hematology P.C ( Site 8000)
Albany, New York, United States
Monter Cancer Center ( Site 0054)
Lake Success, New York, United States
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