A Study of BMS-813160 in Combination With Chemotherapy or 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 evaluate the safety profile, tolerability, drug levels, drug effects, and preliminary efficacy of BMS-813160 alone or in combination with either chemotherapy or nivolumab or chemotherapy plus nivolumab in participants with metastatic colorectal and pancreatic cancers.

Official Title
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A Phase 1b/2 Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors

Conditions
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Colorectal Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: BMS-813160
* Biological: Nivolumab
* Drug: Nab-paclitaxel
* Drug: Gemcitabine
* Drug: 5-fluorouracil (5-FU)
* Drug: Leucovorin
* Drug: Irinotecan


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: Must have metastatic colorectal or pancreatic cancer Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Ability to swallow pills or capsules Required to undergo mandatory pre and on-treatment biopsies Adequate marrow function Adequate other organ functions Ability to comply with study visits, treatment, procedures, pharmacokinetic (PK) and pharmacodynamic (PD) sample collection, and required study follow-up Exclusion Criteria: Histology other than adenocarcinoma (neuroendocrine or acinar cell) Suspected, known, or central nervous system (CNS) metastases (Imaging required only if participants are symptomatic) Active, known or suspected autoimmune disease Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity Prior treatment with cysteine-cysteine chemokine receptor 2 (CCR2) and/or cysteine-cysteine chemokine receptor 5 (CCR5) inhibitors, programmed death-1 receptor (PD-1), programmed death-ligand 1 [PD(L)-1] or cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies History of allergy to study treatments or any of its components of the study arm that participant is enrolling 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 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI<br>FOLFIRI: FOL (folinic acid [leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]) | Drug: BMS-813160<br>* Specified dose on specified days<br>Drug: 5-fluorouracil (5-FU)<br>* Specified dose on specified days<br>Drug: Leucovorin<br>* Specified dose on specified days<br>Drug: Irinotecan<br>* Specified dose on specified days<br>|
| Experimental: Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Drug: Gemcitabine<br>* Specified dose on specified days<br>|
| Experimental: Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab<br>2L: Second-line 2/3L: Second/third-line MSS: Microsatellite stable | Drug: BMS-813160<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Drug: 5-fluorouracil (5-FU)<br>* Specified dose on specified days<br>Drug: Leucovorin<br>* Specified dose on specified days<br>Drug: Irinotecan<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Drug: 5-fluorouracil (5-FU)<br>* Specified dose on specified days<br>Drug: Leucovorin<br>* Specified dose on specified days<br>Drug: Irinotecan<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI<br> | Drug: 5-fluorouracil (5-FU)<br>* Specified dose on specified days<br>Drug: Leucovorin<br>* Specified dose on specified days<br>Drug: Irinotecan<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Drug: Gemcitabine<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Drug: Gemcitabine<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm B Cohort 3c [1L Pancreatic]: Gemcitabine/Nab-paclitaxel<br> | Drug: Nab-paclitaxel<br>* Specified dose on specified days<br>Drug: Gemcitabine<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm C Cohort 4 [2L Pancreatic]: BMS-813160 + Nivolumab<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2 Arm C Cohort 5 [2/3L Colorectal MSS]: BMS-813160 + Nivolumab<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2 Arm D Cohort 7 [2L Pancreatic]: BMS-813160 Monotherapy<br> | Drug: BMS-813160<br>* Specified dose on specified days<br>|
| Experimental: Part 2 Arm D Cohort 8 [2/3L Colorectal MSS]: BMS-813160 Monotherapy<br> | Drug: BMS-813160<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 |
| --- | --- | --- |
| Incidence of Adverse events (AEs) | Part 1 only | Approximately 4 years | 
| Incidence of Serious adverse events (SAEs) | Part 1 only | Approximately 4 years | 
| Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria | Part 1 only | Approximately 6 months | 
| Incidence of AEs leading to discontinuation | Part 1 only | Approximately 4 years | 
| Incidence of Death | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | Part 1 only PR interval: The time from the onset of the P wave to the start of the QRS complex | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval | Part 1 only QRS interval: A combination of the Q wave, R wave and S wave, the QRS complex represents ventricular depolarization | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval | Part 1 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval | Part 1 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF) | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Body temperature | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Respiratory rate | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Pulse oximetry | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Blood pressure | Part 1 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Heart rate | Part 1 only | Approximately 4 years | 
| Decrease in regulatory T cells (Treg) or tumor-associated macrophage (TAM) in tumor samples | Part 1 only | Approximately 4 years | 
| Overall response rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Part 2 only | Approximately 2 years | 
| Median duration of response (DOR) | Part 2 only | Approximately 2 years | 
| Progression free survival (PFS) rate | Part 2 only | At 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Part 1 only | Approximately 2 years | 
| Median duration of response (DOR) | Part 1 only | Approximately 2 years | 
| Progression free survival (PFS) rate | Part 1 only | At 24 weeks | 
| Maximum observed plasma concentration (Cmax) | Part 1 only | Approximately 4 years | 
| Time of maximum observed plasma concentration (Tmax) | Part 1 only | Approximately 4 years | 
| Trough observed plasma concentration (Ctrough) | Part 1 only | Approximately 4 years | 
| Observed plasma concentration at 24 hours post dose (C24) | Part 1 only | Approximately 4 years | 
| Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] | Part 1 only | Approximately 4 years | 
| Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)] | Part 1 only | Approximately 4 years | 
| Apparent total body clearance (CLT/F) | Part 1 only | Approximately 4 years | 
| Accumulation index, calculated based on ratio of AUC(0-24) and Cmax at steady state to after the first dose (AI) | Part 1 only | Approximately 4 years | 
| Renal clearance (CLR) | Part 1 only | Approximately 4 years | 
| Percent urinary recovery over 24 hours corrected for molecular weight (%UR) | Part 1 only | Approximately 4 years | 
| Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) | Part 1 only | Approximately 4 years | 
| Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight [MR_AUC(0-24)] | Part 1 only | Approximately 4 years | 
| Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy | Part 1 only | Approximately 4 years | 
| Incidence of Adverse events (AEs) | Part 2 only | Approximately 4 years | 
| Incidence of Serious adverse events (SAEs) | Part 2 only | Approximately 4 years | 
| Incidence of AEs leading to discontinuation | Part 2 only | Approximately 4 years | 
| Incidence of Death | Part 2 only | Approximately 4 years | 
| Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria | Part 2 Cohort 3b only | Approximately 6 months | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Body temperature | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Respiratory rate | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Pulse oximetry | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Blood pressure | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in vital signs: Heart rate | Part 2 only | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | Part 2 only PR interval: The time from the onset of the P wave to the start of the QRS complex | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval | Part 2 only QRS interval: A combination of the Q wave, R wave and S wave, the QRS complex represents ventricular depolarization | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval | Part 2 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave | Approximately 4 years | 
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval | Part 2 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF) | Approximately 4 years | 
| Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples | Part 2 only | Approximately 4 years |