A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors
- 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
- 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
- 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 Number of Participants Experiencing Adverse Events (AEs) From first dose up to 100 days post last dose, up to approximately 3 years An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Number of Participants Experiencing Serious Adverse Events (SAEs) From first dose up to 100 days post last dose, up to approximately 3 years A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) From first dose up to 100 days post last dose, up to approximately 3 years Dose-limiting toxicities (DLTs) are severe adverse effects (AEs) that are attributed to BMS-813160 or the combination regimen and define the maximum tolerated dose of a medicine. DLTs will be defined based on the incidence, duration and grade of AEs for which no alternate cause can be identified. AEs will be evaluated according to the NCI CTCAE v4.03. The incidence of DLT(s) during the first 6 weeks of treatment in Part 1 (the DLT evaluation period) and 4 weeks for Part 2 will be used.
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation From first dose up to 100 days post last dose, up to approximately 3 years An Adverse Event (AE) leading to discontinuation is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment that leads to the discontinuation of study treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Number of Participants Who Died From first dose up to 100 days post last dose, up to approximately 3 years The number of participants who died within 100 days after receiving their last dose
Number of Participants Experiencing Laboratory Abnormalities From first dose up to 100 days post last dose, up to approximately 3 years The number of participants experiencing laboratory abnormalities in pre-specified selected parameters during the treatment period per CTCAE (Version 4). Laboratory abnormalities are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Vital Signs From first dose to 100 days post last dose, up to approximately 3 years Vital sign measurements at baseline and at the end of treatment. Baseline evaluations will be defined as evaluations with a date on or prior to the day of first dose of study treatment.
Number of Participants With Out-of-Range Electrocardiograms (ECG) From baseline up to 100 days post last dose The number of participants with ECG measurements outside of the range pre-specified in the protocol.
Percent Change in Regulatory T Cells (Treg) in Tumor Samples From first dose up to prespecified timepoints listed below (C0D7; C0D14; C1D1; C1D15; C1D16; C1D28; C2D1) The percent change in Regulatory T Cells (Treg) were taken at prespecified timepoints. Baseline is defined as the last non-missing value prior to the first dosing.
Percent Change in Tumor-Associated Macrophages (TAMs) in Tumor Samples From first dose up to prespecified timepoints listed below (C0D7; C0D14; C1D1; C1D15; C1D16; C1D28; C2D1) The percent change in Tumor-Associated Macrophages (TAMs) were taken at prespecified timepoints. Baseline is defined as the last non-missing value prior to the first dosing.
Objective Response Rate (ORR) From first dose until disease progression, or the last response recorded (up to approximately 5 years) Objective Response Rate (ORR) as determined by Investigator was defined as the number of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) (per RECIST 1.1 criteria) divided by the number of all treated participants. Progression is defined as at least 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm.
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. Complete response (CR)= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response (PR)= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.Duration of Response (DoR) From first dose up to date of disease progression or death, whichever occurs first (up to approximately 5 years) Duration of Response (DOR), computed for all treated participants with a best overall response (BOR) of complete response (CR) or partial response (PR), is defined as the time between the date of first response (CR or PR) and the date of first documented disease progression as determined by RECIST 1.1 or death due to any cause, whichever occurs first, ie., DOR = disease progression date/death date -first response date + 1. For participants who remain alive and have not progressed, DOR will be censored on the date of their last tumor assessment.
CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.Progression Free Survival (PFS) Rate at 24 Weeks From first dose up to Week 24 PFS rate is defined as the proportion of participants who were progression free at Week 24. PFS is defined as the time from first dose to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Progression is defined at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm.
Complete response (CR)= Disappearance of all target lesions. Pathological lymph nodes must have short axis reduction to \< 10 mm. Partial response (PR)= At least 30% decrease in sum of diameters of target lesions.
Participants who died w/o prior progression were considered progressed on death date. Those alive and not progressed were censored on the last tumor assessment date. Those who started subsequent therapy without reported progression were censored at last tumor assessment prior to subsequent therapy. Those without post-baseline tumor assessment and alive were censored at first dose.
- Secondary Outcome Measures
Name Time Method Maximim Concentration (Cmax) From first dose up to the prespecified timepoints, C0D1, C0D14, and C2D1 Cmax is defined as the maximum plasma concentration of the analytes at the prespecified timepoints.
Time to Maximum Concentration (Tmax) From first dose up to the prespecified timpoints, C0D1, C0D14, AND C2D1 Tmax is defined as the time in hours of the maximum observed plasma concentration
Trough Observed Plasma Concentration (Ctrough) From first dose up to prespecified timepoints, C0D1, C5D1, C0D1, C1D15, C5D1 Ctrough is defined as the concentration reached by a drug immediately before the next dose is administered
Area Under Curve (AUC) 0-8 From first dose up to prespecified timepoints- C0D1, C2D1 Area Under Curve (AUC) is defined as the area under the plot of plasma concentration of a drug versus time after dosage measured at 8 hours post-dose
Area Under Curve (AUC) 0-24 From first dose up to prespecified timepoints-C0D1, C2D1 Area Under Curve (AUC) is defined as the area under the plot of plasma concentration of a drug versus time after dosage measured at 8 hours post-dose
Apparent Total Body Clearance (CLT/F) From first dose up to prespecified timepoints-C0D1, C2D14 The total body clearance (CLT/F) is defined as the volume of plasma completely cleared of drug per unit time
Renal Clearance (CLR) From first dose up to prespecified timepoints-C0D1, C0D14 Renal clearance is defined as the rate at which the analytes were removed from the plasma by the kidneys.
Number of Participants Who Were Anti-Drug Antibody (ADA) Positive From first dose up to prespecified timepoints-C1D1, C1D15, C2D1, C3D1, C5D1, C9D1 The number of participants who are anti-drug antibody positive. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment. ADA-positive sample is in a participant who is baseline ADA negative or with an ADA titer to be at least 4-fold or greater than baseline positive titer.
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 D.C., District of Columbia, United States
Local Institution - 0048
🇺🇸Brooksville, Florida, United States
Local Institution - 0047
🇺🇸St. Petersburg, Florida, United States
Local Institution - 0005
🇺🇸Baltimore, Maryland, United States
Scroll for more (30 remaining)Local Institution - 0003🇺🇸Birmingham, Alabama, United States