A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors
Phase 1
Completed
- Conditions
- Pancreatic CancerColorectal Cancer
- Interventions
- Registration Number
- NCT03184870
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 332
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI 5-fluorouracil (5-FU) FOLFIRI: FOL (folinic acid \[leucovorin\]) F (fluorouracil \[5-fluorouracil\]) IRI (irinotecan \[CAMPTOSAR\]) Part 2 Arm B Cohort 3c [1L Pancreatic]: Gemcitabine/Nab-paclitaxel Nab-paclitaxel - Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI 5-fluorouracil (5-FU) - Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel Nab-paclitaxel - Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI 5-fluorouracil (5-FU) - Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab Nivolumab 2L: Second-line 2/3L: Second/third-line MSS: Microsatellite stable Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI 5-fluorouracil (5-FU) - Part 2 Arm C Cohort 5 [2/3L Colorectal MSS]: BMS-813160 + Nivolumab Nivolumab - Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel Nab-paclitaxel - Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel Nab-paclitaxel - Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel Nivolumab - Part 2 Arm C Cohort 4 [2L Pancreatic]: BMS-813160 + Nivolumab Nivolumab - Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel BMS-813160 - Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel Gemcitabine - Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI BMS-813160 FOLFIRI: FOL (folinic acid \[leucovorin\]) F (fluorouracil \[5-fluorouracil\]) IRI (irinotecan \[CAMPTOSAR\]) Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI Leucovorin FOLFIRI: FOL (folinic acid \[leucovorin\]) F (fluorouracil \[5-fluorouracil\]) IRI (irinotecan \[CAMPTOSAR\]) Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI Irinotecan FOLFIRI: FOL (folinic acid \[leucovorin\]) F (fluorouracil \[5-fluorouracil\]) IRI (irinotecan \[CAMPTOSAR\]) Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI BMS-813160 - Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI Leucovorin - Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI Irinotecan - Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI Leucovorin - Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI Irinotecan - Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI Leucovorin - Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI Irinotecan - Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel Gemcitabine - Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel Gemcitabine - Part 2 Arm B Cohort 3c [1L Pancreatic]: Gemcitabine/Nab-paclitaxel Gemcitabine - Part 2 Arm C Cohort 4 [2L Pancreatic]: BMS-813160 + Nivolumab BMS-813160 - Part 2 Arm D Cohort 7 [2L Pancreatic]: BMS-813160 Monotherapy BMS-813160 - Part 2 Arm C Cohort 5 [2/3L Colorectal MSS]: BMS-813160 + Nivolumab BMS-813160 - Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel BMS-813160 - Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab BMS-813160 2L: Second-line 2/3L: Second/third-line MSS: Microsatellite stable Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI BMS-813160 - Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel BMS-813160 - Part 2 Arm D Cohort 8 [2/3L Colorectal MSS]: BMS-813160 Monotherapy BMS-813160 -
- Primary Outcome Measures
Name Time Method Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria Approximately 6 months Part 1 only
Incidence of Serious adverse events (SAEs) Approximately 4 years Part 1 only
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval Approximately 4 years Part 1 only QRS interval: A combination of the Q wave, R wave and S wave, the "QRS complex" represents ventricular depolarization
Incidence of clinically significant changes in vital signs: Body temperature Approximately 4 years Part 1 only
Incidence of clinically significant changes in vital signs: Pulse oximetry Approximately 4 years Part 1 only
Incidence of AEs leading to discontinuation Approximately 4 years Part 1 only
Decrease in regulatory T cells (Treg) or tumor-associated macrophage (TAM) in tumor samples Approximately 4 years Part 1 only
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests Approximately 4 years Part 1 only
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests Approximately 4 years Part 1 only
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval Approximately 4 years Part 1 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave
Incidence of clinically significant changes in vital signs: Respiratory rate Approximately 4 years Part 1 only
Median duration of response (DOR) Approximately 2 years Part 2 only
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval Approximately 4 years Part 1 only PR interval: The time from the onset of the P wave to the start of the QRS complex
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval Approximately 4 years Part 1 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
Incidence of clinically significant changes in clinical laboratory results: Hematology tests Approximately 4 years Part 1 only
Incidence of clinically significant changes in vital signs: Blood pressure Approximately 4 years Part 1 only
Incidence of clinically significant changes in vital signs: Heart rate Approximately 4 years Part 1 only
Overall response rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Approximately 2 years Part 2 only
Progression free survival (PFS) rate At 24 weeks Part 2 only
Incidence of Death Approximately 4 years Part 1 only
Incidence of Adverse events (AEs) Approximately 4 years Part 1 only
- Secondary Outcome Measures
Name Time Method Median duration of response (DOR) Approximately 2 years Part 1 only
Trough observed plasma concentration (Ctrough) Approximately 4 years Part 1 only
Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] Approximately 4 years Part 1 only
Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)] Approximately 4 years Part 1 only
Apparent total body clearance (CLT/F) Approximately 4 years Part 1 only
Renal clearance (CLR) Approximately 4 years Part 1 only
Accumulation index, calculated based on ratio of AUC(0-24) and Cmax at steady state to after the first dose (AI) Approximately 4 years Part 1 only
Percent urinary recovery over 24 hours corrected for molecular weight (%UR) Approximately 4 years Part 1 only
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests Approximately 4 years Part 2 only
Overall response rate (ORR) Approximately 2 years Part 1 only
Progression free survival (PFS) rate At 24 weeks Part 1 only
Maximum observed plasma concentration (Cmax) Approximately 4 years Part 1 only
Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) Approximately 4 years Part 1 only
Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight [MR_AUC(0-24)] Approximately 4 years Part 1 only
Incidence of Adverse events (AEs) Approximately 4 years Part 2 only
Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy Approximately 4 years Part 1 only
Incidence of AEs leading to discontinuation Approximately 4 years Part 2 only
Time of maximum observed plasma concentration (Tmax) Approximately 4 years Part 1 only
Observed plasma concentration at 24 hours post dose (C24) Approximately 4 years Part 1 only
Incidence of Death Approximately 4 years Part 2 only
Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria Approximately 6 months Part 2 Cohort 3b only
Incidence of clinically significant changes in clinical laboratory results: Hematology tests Approximately 4 years Part 2 only
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests Approximately 4 years Part 2 only
Incidence of clinically significant changes in vital signs: Body temperature Approximately 4 years Part 2 only
Incidence of clinically significant changes in vital signs: Respiratory rate Approximately 4 years Part 2 only
Incidence of clinically significant changes in vital signs: Pulse oximetry Approximately 4 years Part 2 only
Incidence of clinically significant changes in vital signs: Heart rate Approximately 4 years Part 2 only
Incidence of clinically significant changes in vital signs: Blood pressure Approximately 4 years Part 2 only
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval Approximately 4 years Part 2 only PR interval: The time from the onset of the P wave to the start of the QRS complex
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval Approximately 4 years Part 2 only QRS interval: A combination of the Q wave, R wave and S wave, the "QRS complex" represents ventricular depolarization
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval Approximately 4 years Part 2 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave
Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples Approximately 4 years Part 2 only
Incidence of Serious adverse events (SAEs) Approximately 4 years Part 2 only
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval Approximately 4 years Part 2 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
Trial Locations
- Locations (40)
Local Institution - 0003
🇺🇸Birmingham, Alabama, United States
Local Institution - 0026
🇺🇸Phoenix, Arizona, United States
Local Institution - 0002
🇺🇸Los Angeles, California, United States
Local Institution - 0025
🇺🇸Los Angeles, California, United States
Local Institution - 0041
🇺🇸Orange, California, United States
Local Institution - 0015
🇺🇸Aurora, Colorado, United States
Local Institution - 0018
🇺🇸Washington, District of Columbia, United States
Local Institution - 0048
🇺🇸Brooksville, Florida, United States
Local Institution - 0047
🇺🇸Saint Petersburg, Florida, United States
Local Institution - 0005
🇺🇸Baltimore, Maryland, United States
Scroll for more (30 remaining)Local Institution - 0003🇺🇸Birmingham, Alabama, United States