Clinical trial NCT03184870: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Pancreatic Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of Adverse events (AEs)
timeFrame: Approximately 4 years
measure: Incidence of Serious adverse events (SAEs)
timeFrame: Approximately 4 years
measure: Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria
timeFrame: Approximately 6 months
measure: Incidence of AEs leading to discontinuation
timeFrame: Approximately 4 years
measure: Incidence of Death
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Body temperature
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Respiratory rate
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Pulse oximetry
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Blood pressure
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Approximately 4 years
measure: Decrease in regulatory T cells (Treg) or tumor-associated macrophage (TAM) in tumor samples
timeFrame: Approximately 4 years
measure: Overall response rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 2 years
measure: Median duration of response (DOR)
timeFrame: Approximately 2 years
measure: Progression free survival (PFS) rate
timeFrame: At 24 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Approximately 2 years
measure: Median duration of response (DOR)
timeFrame: Approximately 2 years
measure: Progression free survival (PFS) rate
timeFrame: At 24 weeks
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Approximately 4 years
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Approximately 4 years
measure: Trough observed plasma concentration (Ctrough)
timeFrame: Approximately 4 years
measure: Observed plasma concentration at 24 hours post dose (C24)
timeFrame: Approximately 4 years
measure: Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)]
timeFrame: Approximately 4 years
measure: Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)]
timeFrame: Approximately 4 years
measure: Apparent total body clearance (CLT/F)
timeFrame: Approximately 4 years
measure: Accumulation index, calculated based on ratio of AUC(0-24) and Cmax at steady state to after the first dose (AI)
timeFrame: Approximately 4 years
measure: Renal clearance (CLR)
timeFrame: Approximately 4 years
measure: Percent urinary recovery over 24 hours corrected for molecular weight (%UR)
timeFrame: Approximately 4 years
measure: Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax)
timeFrame: Approximately 4 years
measure: Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight [MR_AUC(0-24)]
timeFrame: Approximately 4 years
measure: Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy
timeFrame: Approximately 4 years
measure: Incidence of Adverse events (AEs)
timeFrame: Approximately 4 years
measure: Incidence of Serious adverse events (SAEs)
timeFrame: Approximately 4 years
measure: Incidence of AEs leading to discontinuation
timeFrame: Approximately 4 years
measure: Incidence of Death
timeFrame: Approximately 4 years
measure: Incidence of AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria
timeFrame: Approximately 6 months
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Body temperature
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Respiratory rate
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Pulse oximetry
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Blood pressure
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
timeFrame: Approximately 4 years
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF interval
timeFrame: Approximately 4 years
measure: Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples
timeFrame: Approximately 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0003
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 0026
state: Arizona
city: Los Angeles
country: United States
facility: Local Institution - 0002
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0025
state: California
city: Orange
country: United States
facility: Local Institution - 0041
state: California
city: Aurora
country: United States
facility: Local Institution - 0015
state: Colorado
city: Washington
country: United States
facility: Local Institution - 0018
state: District of Columbia
city: Brooksville
country: United States
facility: Local Institution - 0048
state: Florida
city: Saint Petersburg
country: United States
facility: Local Institution - 0047
state: Florida
city: Baltimore
country: United States
facility: Local Institution - 0005
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0033
state: Massachusetts
city: Rochester
country: United States
facility: Local Institution - 0027
state: Minnesota
city: Hattiesburg
country: United States
facility: Local Institution - 0039
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution - 0023
state: Missouri
city: Hackensack
country: United States
facility: Local Institution - 0004
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0017
state: New York
city: Rochester
country: United States
facility: Local Institution - 0024
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0046
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0044
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0021
state: Ohio
city: Allentown
country: United States
facility: Local Institution - 0037
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0014
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0020
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0045
state: South Carolina
city: Nashville
country: United States
facility: Local Institution - 0034
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0038
state: Tennessee
city: Salt Lake City
country: United States
facility: Local Institution - 0016
state: Utah
city: Charlottesville
country: United States
facility: Local Institution - 0042
state: Virginia
city: Clayton
country: Australia
facility: Local Institution - 0028
state: Victoria
city: Bruxelles
country: Belgium
facility: Local Institution - 0050
city: Edegem
country: Belgium
facility: Local Institution - 0051
city: Leuven
country: Belgium
facility: Local Institution - 0049
city: Edmonton
country: Canada
facility: Local Institution - 0013
state: Alberta
city: Ottawa
country: Canada
facility: Local Institution - 0012
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0001
state: Ontario
city: Dresden
country: Germany
facility: Local Institution - 0022
city: Heidelberg
country: Germany
facility: Local Institution - 0007
city: Barcelona
country: Spain
facility: Local Institution - 0031
city: Madrid
country: Spain
facility: Local Institution - 0032
city: Majadahonda - Madrid
country: Spain
facility: Local Institution - 0030
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: