First-In-Human Study of Monoclonal Antibody BMS-986218 by Itself and in Combination With Nivolumab in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether BMS-986218 both by itself and in combination with Nivolumab is safe and tolerable in the treatment of advanced solid tumors.

Official Title
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Phase 1/2a First-In-Human Study of BMS-986218 Monoclonal Antibody Alone and in Combination With Nivolumab in Advanced Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: Ipilimumab
* Biological: BMS-986218
* Biological: Nivolumab


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: Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) Eastern Cooperative Oncology Group Performance Status of 0 or 1 Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists Advanced stage cutaneous melanoma who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-programmed cell death 1 (anti-PD-1) or anti-programmed death ligand 1 (anti-PD-L1) (For Part 2A) Non-small cell lung cancer (NSCLC) (adenocarcinoma or squamous cell carcinoma) who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-PD-1 or anti-PD-L1 (For Parts 2B & 2C) Microsatellite Stable Colorectal Cancer (MSS CRC) who have received standard therapies with proven survival benefit (Part 2D) Exclusion Criteria: Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy Prior anti-cancer treatments such as chemotherapy, radiotherapy, hormonal, or immunotherapy (including anti-PD-1/PD-L1) are permitted 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: Part 1A: Monotherapy (BMS-986218)<br> | Biological: BMS-986218<br>* Specified dose on specified days<br>|
| Experimental: Part 1B: Combination Therapy (BMS-986218 + Nivolumab)<br> | Biological: BMS-986218<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 2A: Monotherapy (BMS-986218 OR Ipilimumab)<br> | Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;Biological: BMS-986218<br>* Specified dose on specified days<br>|
| Experimental: Part 2B: Monotherapy (BMS-986218)<br> | Biological: BMS-986218<br>* Specified dose on specified days<br>|
| Experimental: Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab)<br> | Biological: BMS-986218<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab)<br> | Biological: BMS-986218<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | Up to 2 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 2 years | 
| Incidence of AEs meeting protocol- defined dose-limiting toxicity (DLT) criteria |  | Up to 2 years | 
| Incidence of AEs leading to discontinuation |  | Up to 2 years | 
| Incidence of death |  | Up to 2 years | 
| Objective Response Rate (ORR) | Parts 2A, 2B, 2C and 2D | Up to 4 years | 
| Median Duration of Response (mDOR) | Parts 2A, 2B, 2C and 2D | Up to 4 years | 
| Progression Free Survival Rate (PFSR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Parts 2A, 2B, 2C and 2D | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Parts 1A and 1B | Up to 4 years | 
| mDOR | Parts 1A and 1B | Up to 4 years | 
| PFSR by RECIST v1.1 | Parts 1A and 1B | Up to 4 years | 
| Incidence of anti-drug antibody (ADA) |  | Up to 4 years | 
| Maximum observed plasma concentration (Cmax) |  | Up to 4 years | 
| Time of maximum observed plasma concentration (Tmax) |  | Up to 4 years | 
| Trough observed serum concentration (Ctrough) |  | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nivolumab, BMS-986218, Ipilimumab