The main purpose of this study was to evaluate safety and efficacy in participants treated with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT plus placebo followed by durvalumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
153
Participants received intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
Participants received intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
Participants received intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
PFS was defined as the time from randomization to the date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was analyzed by using the Kaplan-Meier method.
Time frame: Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention.
Time frame: Time from randomization up to data cut off (assessed up to 27 months)
Overall Survival (OS)
Overall Survival was defined as the time from randomization to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.
Time frame: Time from randomization to the date of death due to any cause, assessed up to 27 months
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
ORR was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to RECIST v1.1as adjudicated by the Investigator. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions.
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Participants received etoposide 50 mg/m\^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.
Participants received pemetrexed at a dose of 500 mg/m\^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.
Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.
Participants received paclitaxel intravenously at a dose of 45 mg/m\^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.
In combination with etoposide, participants received cisplatin 50 mg/m\^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.
Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray \[Gy\]).
University of California Irvine Medical Center
Orange, California, United States
UCLA Hematology Oncology - Main Site - 2020 Santa Monica
Santa Monica, California, United States
University of Colorado Health - Memorial Hospital - Memorial Hospital
Colorado Springs, Colorado, United States
Hematology Oncology Associates
Fort Collins, Colorado, United States
Lynn Cancer Institute Center
Boca Raton, Florida, United States
Holy Cross Hospital - Michael and Dianne Bienes CCC
Fort Lauderdale, Florida, United States
Sylvester Comprehensive Cancer Center - University of Miami Health System
Miami, Florida, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
American Health Network of Indiana, LLC
Indianapolis, Indiana, United States
Franciscan St. Francis Health Cancer Center
Indianapolis, Indiana, United States
...and 94 more locations
Time frame: Time from randomization up to data cut off (assessed up to 27 months)
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
DOR was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.
Time frame: Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed approximately up to 27 months
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824
Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed M7824 concentration-time data.
Time frame: Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824
Ctrough was the serum concentration observed immediately before next dosing.
Time frame: Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Number of Participants With Positive Antidrug Antibodies (ADA)
Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.
Time frame: Time from randomization up to data cut off (assessed up to 27 months)