Description:
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.
Title
- Brief Title: A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors
- Official Title: A Phase 1b/2 Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
CV202-103
- SECONDARY ID:
2017-001725-40
- NCT ID:
NCT03184870
Conditions
- Colorectal Cancer
- Pancreatic Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| BMS-813160 | | Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI |
| Nivolumab | Opdivo, BMS-936558 | Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab |
| Nab-paclitaxel | | Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel |
| Gemcitabine | | Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel |
| 5-fluorouracil (5-FU) | | Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI |
| Leucovorin | | Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI |
| Irinotecan | | Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI | Experimental | FOLFIRI: FOL (folinic acid [leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR]) | - BMS-813160
- 5-fluorouracil (5-FU)
- Leucovorin
- Irinotecan
|
| Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel | Experimental | | - BMS-813160
- Nab-paclitaxel
- Gemcitabine
|
| Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab | Experimental | 2L: Second-line 2/3L: Second/third-line MSS: Microsatellite stable | |
| Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI | Experimental | | - BMS-813160
- 5-fluorouracil (5-FU)
- Leucovorin
- Irinotecan
|
| Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI | Experimental | | - BMS-813160
- 5-fluorouracil (5-FU)
- Leucovorin
- Irinotecan
|
| Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI | Experimental | | - 5-fluorouracil (5-FU)
- Leucovorin
- Irinotecan
|
| Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel | Experimental | | - BMS-813160
- Nab-paclitaxel
- Gemcitabine
|
| Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel | Experimental | | - BMS-813160
- Nivolumab
- Nab-paclitaxel
- Gemcitabine
|
| Part 2 Arm B Cohort 3c [1L Pancreatic]: Gemcitabine/Nab-paclitaxel | Experimental | | - Nab-paclitaxel
- Gemcitabine
|
| Part 2 Arm C Cohort 4 [2L Pancreatic]: BMS-813160 + Nivolumab | Experimental | | |
| Part 2 Arm C Cohort 5 [2/3L Colorectal MSS]: BMS-813160 + Nivolumab | Experimental | | |
| Part 2 Arm D Cohort 7 [2L Pancreatic]: BMS-813160 Monotherapy | Experimental | | |
| Part 2 Arm D Cohort 8 [2/3L Colorectal MSS]: BMS-813160 Monotherapy | Experimental | | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Adverse events (AEs) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
Secondary Outcome Measures
| Measure: | Overall response rate (ORR) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Median duration of response (DOR) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Progression free survival (PFS) rate |
| Time Frame: | At 24 weeks |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Maximum observed plasma concentration (Cmax) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Time of maximum observed plasma concentration (Tmax) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Trough observed plasma concentration (Ctrough) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Observed plasma concentration at 24 hours post dose (C24) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)] |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Apparent total body clearance (CLT/F) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Accumulation index, calculated based on ratio of AUC(0-24) and Cmax at steady state to after the first dose (AI) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Renal clearance (CLR) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Percent urinary recovery over 24 hours corrected for molecular weight (%UR) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight [MR_AUC(0-24)] |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 1 only |
| Measure: | Incidence of Adverse events (AEs) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of Serious adverse events (SAEs) |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of AEs leading to discontinuation |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of Death |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria |
| Time Frame: | Approximately 6 months |
| Safety Issue: | |
| Description: | Part 2 Cohort 3b only |
| Measure: | Incidence of clinically significant changes in clinical laboratory results: Hematology tests |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in vital signs: Body temperature |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in vital signs: Respiratory rate |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in vital signs: Pulse oximetry |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in vital signs: Blood pressure |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in vital signs: Heart rate |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
| Measure: | Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only PR interval: The time from the onset of the P wave to the start of the QRS complex |
| Measure: | Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only QRS interval: A combination of the Q wave, R wave and S wave, the "QRS complex" represents ventricular depolarization |
| Measure: | Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave |
| Measure: | Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF) |
| Measure: | Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples |
| Time Frame: | Approximately 4 years |
| Safety Issue: | |
| Description: | Part 2 only |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
April 20, 2021
