A Clinical Study Evaluating Nivolumab-containing Treatments in Patients With Advanced Non-small Cell Lung Cancer After Failing Previous PD-1/(L)1 Therapy and Chemotherapy

Study Overview
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Brief Summary
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This study is for participants with Non-small Cell Lung Cancer that has spread or has reoccurred after failure of Chemotherapy and Immunotherapy

Official Title
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A Phase 1/2, Randomized Study Evaluating Multiple Nivolumab Combination Therapies in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) After Failure of Platinum-Based Chemotherapy and Anti-PD-1 (L)1 Immunotherapy

Conditions
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Carcinoma, Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: nivolumab
* Biological: ipilimumab
* Drug: cabozantinib
* Biological: docetaxel
* Biological: ramucirumab
* Drug: lucitanib


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria Histologically or cytologically-documented Stage IV A/B non-small cell lung Cancer, stage IIIB/C disease failed concurrent chemoRT. ECOG Performance Status of ≤ 1. Radiologically-documented disease progression on one anti-PD-1/anti-PD-L1 therapy and one platinum-based doublet regimen given either concurrently or sequentially within 90 days after the last dose of anti-PD-(L)1. All participants must have tumor tissue submitted prior to randomization, either a recent archival sample obtained on/after the date of disease progression of the last prior anticancer therapy and within 3 months prior to enrollment, or a fresh biopsy obtained during the screening period. Prior toxicities must have resolved to grade ≤1. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test and must not be breastfeeding. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception. In addition, male participants must be willing to refrain from sperm donation during this time and must agree to follow instructions for method(s) of contraception. Azoospermic males are exempt from contraceptive requirements as well as WOCBP who are continuously not heterosexually active, however, a pregnancy test will still be required. Exclusion Criteria Prior treatment with Docetaxel. Untreated CNS metastases, carcinomatous meningitis or leptomeningeal metastases. Any tumor invading the Superior Vena Cava other blood vessel, GI Tract or Trachea. EGFR mutations, ALK translocations, ROS1 translocations which are sensitive to inhibitor therapy. History of cerebrovascular accident and coagulation disorders. Participants with interstitial lung disease, history of cerebrovascular accident or history of abdominal fistula, gastrointestinal perforation, bowel obstruction, intra-abdominal abscess or grade 3-4 bleeding event within 6 months prior to randomization. Known toxicity on prior checkpoint inhibitor treatment. Participants who received more than one line of anti- PD-1/PD-L1 treatment. Participants who received previous CTLA-4 inhibitor treatment. Participants with known BRAF V600E mutation which are sensitive to available targeted inhibitor therapy are excluded. Other protocol-defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: cabozantinib + nivolumab + ipilimumab<br> | Biological: nivolumab<br>* Specified dose on Specified days<br>* Other names: BMS-936558;Biological: ipilimumab<br>* Specified dose on Specified days<br>* Other names: YERVOY;Drug: cabozantinib<br>* Specified dose on Specified days<br>* Other names: CABOMETYX;|
| Experimental: Arm B: cabozantinib + nivolumab<br> | Biological: nivolumab<br>* Specified dose on Specified days<br>* Other names: BMS-936558;Drug: cabozantinib<br>* Specified dose on Specified days<br>* Other names: CABOMETYX;|
| Experimental: Arm C: nivolumab + ramucirumab + docetaxel<br> | Biological: nivolumab<br>* Specified dose on Specified days<br>* Other names: BMS-936558;Biological: docetaxel<br>* Specified dose on Specified days<br>Biological: ramucirumab<br>* Specified dose on Specified days<br>* Other names: CYRAMZA;|
| Experimental: Arm D: lucitanib + nivolumab<br> | Biological: nivolumab<br>* Specified dose on Specified days<br>* Other names: BMS-936558;Drug: lucitanib<br>* Specified dose on Specified days<br>* Other names: CO-3810;|
| Experimental: Arm E: nivolumab + docetaxel<br> | Biological: nivolumab<br>* Specified dose on Specified days<br>* Other names: BMS-936558;Biological: docetaxel<br>* Specified dose on Specified days<br>|
| Active Comparator: Arm F: docetaxel<br> | Biological: docetaxel<br>* Specified dose on Specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Reponse Rate (ORR) using RECIST 1.1 per Blinded Independent Central Review (BICR) assessment |  | approximately 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Up to 5 Years | 
| Duration of Response (DOR) by BICR using RECIST 1.1 |  | approximately 33 months | 
| Progression-Free Survival (PFS) by BICR using RECIST 1.1 |  | Up to 5 Years | 
| Incidence of Adverse Events (AEs) |  | Up to 5 Years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 5 Years | 
| Incidence of Select AEs |  | Up to 5 Years |