An Investigational Immuno-therapy Study to Test Combination Treatments in Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether Nivolumab, in combination with other therapies, is effective in patients with advanced Non-Small Cell lung cancer

Official Title
-----------------
A Phase 2, Fast Real Time Assessment of Combination Therapies in Immuno-Oncology Study in Subjects With Advanced Non-Small Cell Lung Cancer (FRACTION-Lung)

Conditions
-----------------
Advanced Cancer

Intervention / Treatment
-----------------
* Biological: Nivolumab
* Drug: Dasatinib
* Biological: Relatlimab
* Biological: Ipilimumab
* Drug: BMS-986205


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Advanced Non Small Cell Lung Cancer (NSCLC) Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1 Life expectancy of at least 3 months from most recent chemotherapy or immunotherapy treatment Must have at least 1 lesion with measurable disease Exclusion Criteria: Subjects with certain mutations that have not been treated with a targeted therapy prior to enrollment Subjects who need daily oxygen therapy People with autoimmune disease Other protocol defined inclusion/exclusion criteria could 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 |
| --- | --- |
| Active Comparator: Nivolumab<br>Nivolumab Monotherapy - Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator | Biological: Nivolumab<br>* Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.<br>* Other names: OPDIVO;|
| Experimental: Nivolumab & Dasatinib<br>Nivolumab in combination with Dasatinib | Biological: Nivolumab<br>* Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.<br>* Other names: OPDIVO;Drug: Dasatinib<br> <br> * Other names: SPRYCEL;|
| Experimental: Nivolumab & Relatlimab<br>Nivolumab in combination with Relatlimab | Biological: Nivolumab<br>* Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.<br>* Other names: OPDIVO;Biological: Relatlimab<br> <br> * Other names: BMS-986016;|
| Experimental: Nivolumab & Ipilimumab<br>Nivolumab in combination with Ipilimumab | Biological: Nivolumab<br>* Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.<br>* Other names: OPDIVO;Biological: Ipilimumab<br> <br> * Other names: Yervoy;|
| Experimental: Nivolumab & BMS-986205<br>Nivolumab in combination with BMS- 986205 | Biological: Nivolumab<br>* Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.<br>* Other names: OPDIVO;Drug: BMS-986205<br>* Specified dose on specified days<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants whose confirmed best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR was assessed by investigator per RECIST1.1. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track. | From first dose to 2 years following last dose (up to 30 months) | 
| Duration of Response (DOR) | DOR, computed for all treated participants with a confirmed BOR of CR or PR, is defined as the time between the date of first response and the date of first documented disease progression (as determined by RECIST 1.1) or death due to any cause. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track. | From first dose to 2 years following last dose (up to 30 months) | 
| Progression Free Survival Rate (PFSR) at 24 Weeks | The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive (>=1%) Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative (<1%) Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track. | From first dose to 24 weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Adverse Events (AEs) | This outcome measure describes the percentage of participants who experienced any grade, all causality AEs during the specified time frame | From first dose to 100 days following last dose | 
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) | This outcome measure describes the percentage of participants who experienced any grade, all causality SAEs during the specified time frame | From first dose to 100 days following last dose | 
| Percentage of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | This outcome measure describes the percentage of participants who experienced all causality AEs leading to discontinuation of study therapy during the specified time frame | From first dose to 100 days following last dose | 
| Percentage of Participants Experiencing Death | This outcome measure describes the percentage of participants who died (due to any cause) during the specified time frame | From first dose to up to 45 months following first dose | 
| Number of Participants Experiencing Laboratory Abnormalities in Hepatic Tests | The following measurements will be considered laboratory abnormalities for hepatic tests: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN ALT=Alanine aminotransferase AST=Aspartate aminotransferase ULN=Upper Limit of Normal | From first dose to 100 days following last dose (approximately 9 months) | 
| Number of Participants Experiencing Laboratory Abnormalities in Thyroid Tests | The following measurements will be considered laboratory abnormalities for thyroid tests: TSH value > ULN and With baseline TSH value ≤ ULN At least one T3/T4 test value < LLN Low TSH < LLN and With baseline TSH value ≥ LLN At least one T3/T4 test value > ULN TSH = thyroid stimulating hormone ULN=Upper Limit of Normal LLN=Lower Limit of Normal T3=Triiodothyronine T4=Thyroxine | From first dose to 100 days following last dose (approximately 9 months) |