A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease

Official Title
-----------------
A Phase 3, Randomized Study of Nivolumab Plus Ipilimumab in Combination With Chemotherapy vs Chemotherapy Alone as First Line Therapy in Stage IV Non-Small Cell Lung Cancer

Conditions
-----------------
Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Biological: Ipilimumab
* Biological: Nivolumab
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Pemetrexed
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Participants with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period Exclusion Criteria: Participants with known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded Participants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excluded Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment Other protocol inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module A<br>Chemotherapy/Biologics combined | Biological: Ipilimumab<br>* Specified dose on specified day<br>* Other names: Yervoy, BMS734016;Biological: Nivolumab<br>* Specified dose on specified day<br>* Other names: Opdivo, BMS936558;Drug: Carboplatin<br>* Specified dose on specified day<br>Drug: Paclitaxel<br>* Specified dose on specified day<br>* Other names: Taxol;Drug: Pemetrexed<br>* Specified dose on specified day<br>* Other names: Alimta;Drug: Cisplatin<br>* Specified dose on specified day<br>* Other names: Platinol;|
| Active Comparator: Module B<br>Chemotherapy Combination | Drug: Carboplatin<br>* Specified dose on specified day<br>Drug: Paclitaxel<br>* Specified dose on specified day<br>* Other names: Taxol;Drug: Pemetrexed<br>* Specified dose on specified day<br>* Other names: Alimta;Drug: Cisplatin<br>* Specified dose on specified day<br>* Other names: Platinol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. | From date of randomization to date of death (assessed up to October 2019, approximately 23 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) by BICR | PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months) | 
| Objective Response Rate (ORR) by BICR | ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression. | From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) | 
| Duration of Response (DoR) | DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only. | From date of first confirmed response to date of tumor progression (assessed up to October 2019, approximately 23 months) | 
| Time to Response (TTR) | TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only. | From date of randomization to date of first confirmed documented response (assessed up to October 2019, approximately 23 months) | 
| Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression | PD-L1 expression was defined as the percent of tumor cells with membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC 28-8 pharmDx test. PD-L1 expression was classified as PD-L1 ≥1% (≥1% tumor cells with membrane staining in a minimum of a hundred evaluable tumor cells), PD-L1 < 1% and PD-L1 not quantifiable (without quantifiable PD-L1 expression), PD-L1 expression ≥ 50%, PD-L1 expression 1 to 49% | From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) | 
| PFS by BICR by PD-L1 Tumor Cell Expression | PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. | From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months) | 
| OS by PD-L1 Tumor Cell Expression | OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. | From date of randomization to date of death (assessed up to October 2019, approximately 23 months) |