A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
To investigate the safety and efficacy of nivolumab as a single agent or in combination with ipilimumab in 6 tumor types - triple-negative breast cancer (TNBC), gastric cancer (GC), pancreatic adenocarcinoma (PC), small cell lung cancer (SCLC), bladder cancer (BC), and ovarian cancer (OC). A combination of nivolumab with ipilimumab and cobimetinib is also investigated in PC.

Detailed Description
-----------------
All tumor types are now closed for enrollment: Triple Negative Breast Cancer Gastric Cancer Pancreatic Cancer Small Cell Lung Cancer Bladder Cancer Ovarian Cancer

Official Title
-----------------
A Phase 1/2, Open-label Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab in Subjects With Advanced or Metastatic Solid Tumors

Conditions
-----------------
Advanced or Metastatic Solid Tumors

Intervention / Treatment
-----------------
* Biological: Nivolumab
* Biological: Ipilimumab
* Drug: Cobimetinib


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Subjects with histologically or cytologically confirmed locally advanced or metastatic disease of the following tumor types: Triple Negative Breast Cancer Gastric Cancer Pancreatic Cancer Small Cell Lung Cancer Bladder Cancer Ovarian Cancer Subjects must have measurable disease Eastern Cooperative Oncology Group (ECOG) of 0 or 1 Adequate hematological and organ function as confirmed by laboratory values Exclusion Criteria: Active brain metastases or leptomeningeal metastases Subjects with active, known or suspected autoimmune disease Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including Ipilimumab; or other medicines specifically targeting T cell is also prohibited

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: Arm N - Nivolumab<br>Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;|
| Experimental: Arm N-I, Level 1: Nivolumab+Ipilimumab<br>Nivolumab 1 mg/kg solution intravenously plus Ipilimumab 1 mg/kg solution every 3 weeks for 4 doses followed by Nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;Biological: Ipilimumab<br> <br> * Other names: MDX-010;|
| Experimental: Arm N-I, Level 2: Nivolumab+Ipilimumab<br>Nivolumab 1 mg/kg solution intravenously plus Ipilimumab 3 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;Biological: Ipilimumab<br> <br> * Other names: MDX-010;|
| Experimental: Arm N-I, Level 2b: Nivolumab+Ipilimumab<br>Nivolumab 3 mg/kg solution intravenously plus Ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;Biological: Ipilimumab<br> <br> * Other names: MDX-010;|
| Experimental: Arm N-I, Level 2c: Nivolumab+Ipilimumab<br>Nivolumab 3 mg/kg solution intravenously every 3 weeks combined with ipilimumab 1 mg/kg every 6 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;Biological: Ipilimumab<br> <br> * Other names: MDX-010;|
| Experimental: Arm N-I, Level 2d: Nivolumab+Ipilimumab+Cobimetinib<br>Nivolumab 3 mg/kg solution intravenously every 3 weeks combined with ipilimumab 1 mg/kg every 6 weeks and cobimetinib 60mg once daily 21days on/7 days off until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends | Biological: Nivolumab<br> <br> * Other names: MDX-1106;Biological: Ipilimumab<br> <br> * Other names: MDX-010;Drug: Cobimetinib<br> <br> * Other names: Cotellic;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate ( ORR ) | The number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants. | 60 months |