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A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03184870
Recruitment Status : Active, not recruiting
First Posted : June 14, 2017
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE June 9, 2017
First Posted Date  ICMJE June 14, 2017
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE August 8, 2017
Estimated Primary Completion Date February 27, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2021)
  • Incidence of Adverse events (AEs) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of Serious adverse events (SAEs) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria [ Time Frame: Approximately 6 months ]
    Part 1 only
  • Incidence of AEs leading to discontinuation [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of Death [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in clinical laboratory results: Hematology tests [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval [ Time Frame: 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: QRS interval [ Time Frame: 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 electrocardiogram (ECG) parameters: QT interval [ Time Frame: 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 electrocardiogram (ECG) parameters: QTcF interval [ Time Frame: Approximately 4 years ]
    Part 1 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
  • Incidence of clinically significant changes in vital signs: Body temperature [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in vital signs: Respiratory rate [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in vital signs: Pulse oximetry [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in vital signs: Blood pressure [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of clinically significant changes in vital signs: Heart rate [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Decrease in regulatory T cells (Treg) or tumor-associated macrophage (TAM) in tumor samples [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Overall response rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Approximately 2 years ]
    Part 2 only
  • Median duration of response (DOR) [ Time Frame: Approximately 2 years ]
    Part 2 only
  • Progression free survival (PFS) rate [ Time Frame: At 24 weeks ]
    Part 2 only
Original Primary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
  • Adverse events (AEs) [ Time Frame: Approximately 4 years ]
    Measured by incidence of AEs
  • Serious adverse events (SAEs) [ Time Frame: Approximately 4 years ]
    Measured by incidence of SAEs
  • AEs meeting protocol-defined dose limiting toxicity criteria [ Time Frame: Approximately 6 months ]
    Measured by incidence of AEs that meet the protocol-defined dose limiting toxicity criteria
  • AEs leading to discontinuation [ Time Frame: Approximately 4 years ]
    Measured by incidence of AEs leading to discontinuation
  • Death [ Time Frame: Approximately 4 years ]
    Measured by incidence of deaths
  • Incidence of laboratory abnormalities [ Time Frame: Approximately 4 years ]
    Measured by any laboratory test result that is clinically significant or meets the definition of an SAE, any laboratory test result abnormality that required the patient to have study treatment discontinued or interrupted, or any laboratory test result abnormality that required the participant to receive specific corrective therapy
  • Electrocardiogram (ECG) [ Time Frame: Approximately 4 years ]
    ECGs will be evaluated by the investigator for any clinically significant changes or for changes meeting dose modifying criteria.
  • Summary measures of vital signs [ Time Frame: Approximately 4 years ]
    Including weight, body temperature, respiratory rate, pulse oximetry, seated blood pressure and heart rate.
  • Objective response rate (ORR) [ Time Frame: Approximately 4 years ]
    ORR is defined as the proportion of all treated participants whose Best overall response (BOR) is either complete response or partial response. BOR for a participant will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator
  • Median duration of response (DOR) [ Time Frame: Approximately 4 years ]
    DOR for a participant with a BOR of CR or PR, is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1 or death, whichever occurs first
  • Progression free survival (PFS) rate [ Time Frame: At 24 weeks ]
    PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2021)
  • Overall response rate (ORR) [ Time Frame: Approximately 2 years ]
    Part 1 only
  • Median duration of response (DOR) [ Time Frame: Approximately 2 years ]
    Part 1 only
  • Progression free survival (PFS) rate [ Time Frame: At 24 weeks ]
    Part 1 only
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Time of maximum observed plasma concentration (Tmax) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Trough observed plasma concentration (Ctrough) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Observed plasma concentration at 24 hours post dose (C24) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)] [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Apparent total body clearance (CLT/F) [ Time Frame: 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) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Renal clearance (CLR) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Percent urinary recovery over 24 hours corrected for molecular weight (%UR) [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) [ Time Frame: 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)] [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy [ Time Frame: Approximately 4 years ]
    Part 1 only
  • Incidence of Adverse events (AEs) [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of Serious adverse events (SAEs) [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of AEs leading to discontinuation [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of Death [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria [ Time Frame: Approximately 6 months ]
    Part 2 Cohort 3b only
  • Incidence of clinically significant changes in clinical laboratory results: Hematology tests [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in vital signs: Body temperature [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in vital signs: Respiratory rate [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in vital signs: Pulse oximetry [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in vital signs: Blood pressure [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in vital signs: Heart rate [ Time Frame: Approximately 4 years ]
    Part 2 only
  • Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Approximately 4 years ]
    Part 2 only QT interval: Measured from the beginning of the QRS complex to the end of the T wave
  • Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval [ Time Frame: Approximately 4 years ]
    Part 2 only QTcF interval: Corrected QT interval using Fridericia's formula (QTcF)
  • Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples [ Time Frame: Approximately 4 years ]
    Part 2 only
Original Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Time of maximum observed plasma concentration (Tmax) [ Time Frame: Approximately 4 years ]
    Summary statistics: medians and ranges
  • Trough observed plasma concentration (Ctrough) [ Time Frame: Approximately 4 years ]
    Summary statistics to assess attainment of steady state: geometric means and coefficients of variation; plots vs time by dose
  • Observed plasma concentration at the end of the dosing interval (Ctau) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Apparent total body clearance (CLT/F) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Accumulation index, calculated based on ratio of AUC(TAU) and Cmax at steady state to after the first dose (AI) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Renal clearance (CLR) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Percent urinary recovery over 24 hours corrected for molecular weight (%UR) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
  • Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy [ Time Frame: Approximately 4 years ]
    Frequency distribution of baseline ADA-positive participants and ADA-positive participants after initiation of the treatment
  • Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples [ Time Frame: Approximately 4 years ]
    Examination of tumor-associated immune cells and microenvironment, through proteomics
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Participants With Advanced Solid Tumors
Official Title  ICMJE A Phase 1b/2 Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Pancreatic Cancer
Intervention  ICMJE
  • Drug: BMS-813160
    Specified dose on specified days
  • Biological: Nivolumab
    Specified dose on specified days
    Other Names:
    • Opdivo
    • BMS-936558
  • Drug: Nab-paclitaxel
    Specified dose on specified days
  • Drug: Gemcitabine
    Specified dose on specified days
  • Drug: 5-fluorouracil (5-FU)
    Specified dose on specified days
  • Drug: Leucovorin
    Specified dose on specified days
  • Drug: Irinotecan
    Specified dose on specified days
Study Arms  ICMJE
  • Experimental: Part 1 Arm A [First-line (1L) Colorectal]: BMS-813160 followed by BMS-813160 + FOLFIRI
    FOLFIRI: FOL (folinic acid [leucovorin]) F (fluorouracil [5-fluorouracil]) IRI (irinotecan [CAMPTOSAR])
    Interventions:
    • Drug: BMS-813160
    • Drug: 5-fluorouracil (5-FU)
    • Drug: Leucovorin
    • Drug: Irinotecan
  • Experimental: Part 1 Arm B [1L Pancreatic]: BMS-813160 followed by BMS-813160 + Gemcitabine/Nab-paclitaxel
    Interventions:
    • Drug: BMS-813160
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Experimental: Part 1 Arm C [2L Pancreatic & 2/3L Colorectal MSS]: BMS-813160 followed by BMS-813160 + Nivolumab
    2L: Second-line 2/3L: Second/third-line MSS: Microsatellite stable
    Interventions:
    • Drug: BMS-813160
    • Biological: Nivolumab
  • Experimental: Part 2 Arm A Cohort 1a [2L Colorectal]: BMS-813160 + FOLFIRI
    Interventions:
    • Drug: BMS-813160
    • Drug: 5-fluorouracil (5-FU)
    • Drug: Leucovorin
    • Drug: Irinotecan
  • Experimental: Part 2 Arm A Cohort 1b [2L Colorectal]: BMS-813160 + FOLFIRI
    Interventions:
    • Drug: BMS-813160
    • Drug: 5-fluorouracil (5-FU)
    • Drug: Leucovorin
    • Drug: Irinotecan
  • Experimental: Part 2 Arm A Cohort 1c [2L Colorectal]: FOLFIRI
    Interventions:
    • Drug: 5-fluorouracil (5-FU)
    • Drug: Leucovorin
    • Drug: Irinotecan
  • Experimental: Part 2 Arm B Cohort 3a [1L Pancreatic]: BMS-813160 + Gemcitabine/Nab-paclitaxel
    Interventions:
    • Drug: BMS-813160
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Experimental: Part 2 Arm B Cohort 3b [1L Pancreatic]: BMS-813160 + Nivolumab + Gemcitabine/Nab-paclitaxel
    Interventions:
    • Drug: BMS-813160
    • Biological: Nivolumab
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Experimental: Part 2 Arm B Cohort 3c [1L Pancreatic]: Gemcitabine/Nab-paclitaxel
    Interventions:
    • Drug: Nab-paclitaxel
    • Drug: Gemcitabine
  • Experimental: Part 2 Arm C Cohort 4 [2L Pancreatic]: BMS-813160 + Nivolumab
    Interventions:
    • Drug: BMS-813160
    • Biological: Nivolumab
  • Experimental: Part 2 Arm C Cohort 5 [2/3L Colorectal MSS]: BMS-813160 + Nivolumab
    Interventions:
    • Drug: BMS-813160
    • Biological: Nivolumab
  • Experimental: Part 2 Arm D Cohort 7 [2L Pancreatic]: BMS-813160 Monotherapy
    Intervention: Drug: BMS-813160
  • Experimental: Part 2 Arm D Cohort 8 [2/3L Colorectal MSS]: BMS-813160 Monotherapy
    Intervention: Drug: BMS-813160
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 16, 2021)		 332
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2017)		 260
Estimated Study Completion Date  ICMJE February 28, 2023
Estimated Primary Completion Date February 27, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Germany,   Spain,   United States
Removed Location Countries France
 
Administrative Information
NCT Number  ICMJE NCT03184870
Other Study ID Numbers  ICMJE CV202-103
2017-001725-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP