Clinical trial NCT02737475: An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread
Official title: A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination With Nivolumab and/or Ipilimumab in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 166
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 the study is to determine the safety and tumor-shrinking ability of experimental medication BMS-986178, when given by itself or in combination with Nivolumab and/or Ipilimumab, in participants with solid cancers that are advanced or have spread.


Eligibility criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

For Part 9 (only arm open for enrollment):

* Stage IV metastatic or unresectable triple negative breast cancer (TNBC) with zero or one prior systemic therapies in the advanced metastatic setting
* Participants with \< 12 months from receipt of last curative-intent chemotherapy are allowed; curative chemotherapy will be considered first-line therapy
* Prior receipt of chemotherapy in the (neo)adjuvant setting is acceptable, as long as completed greater than 6 months from start of treatment
* Tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required for all participants enrolled
* Must have histologic or cytologic confirmation of a malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
* Men and women must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

* Must be immunotherapy treatment naïve, including no prior therapy with T cell immune checkpoint blocker (anti-PDL1, anti-PD1). Prior receipt of intralymphatic cytokine therapy (IRX-2) is acceptable (Part 9 only)
* Other active malignancy requiring concurrent intervention
* Prior therapy with any agent specifically targeting T-cell co-stimulation pathways such as anti-OX40 antibody, anti-CD137, anti- glucocorticoid-induced TNFR-related gene (anti-GITR) antibody, and anti-CD27
* Known or underlying medical or psychiatric condition and/or social reason that, in the opinion of the investigator or Sponsor, could make the administration of study drug hazardous to the participant or could adversely affect the ability of the participant to comply with or tolerate the study

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
timeFrame: From first dose to 28 days after first dose
measure: The Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose to 100 days after last dose (up to approximately 2.5 years)
measure: The Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first dose to 100 days after last dose (up to approximately 2.5 years)
measure: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose to 100 days after last dose (up to approximately 2.5 years)
measure: The Number of Participant Deaths
timeFrame: From first dose to study completion (up to approximately 4 years 5 months)
measure: The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology)
timeFrame: From baseline to 100 days after last dose (up to approximately 2.5 years)
measure: The Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)
timeFrame: From baseline to 100 days after last dose (up to approximately 2.5 years)
measure: The Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )
timeFrame: From baseline to 100 days after last dose (up to approximately 2.5 years)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From baseline up to approximately 2.5 years
measure: Duration of Response (DOR)
timeFrame: From baseline up to approximately 2.5 years
measure: Progression Free Survival (PFS) Rate at 24 Weeks
timeFrame: 24 weeks after first dose
measure: Cmax: Maximum Observed Serum Concentration
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: Tmax: Time of Maximum Observed Serum Concentration
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: AUC(0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: AUC(TAU): Area Under the Serum Concentration-time Curve in 1 Dosing Interval
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: Ctau: Observed Serum Concentration at the End of a Dosing Interval When Intensive Samples Are Collected
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: CLT: Total Body Clearance
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: Css-avg: Average Concentration Over a Dosing Interval (AUC(TAU)/Tau)
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Cmax)
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (AUC)
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Ctau)
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: T-HALFeff: Effective Elimination Half-life That Explains the Degree of Accumulation Observed for a Specific Exposure Measure (Exposure Measure Includes AUC(TAU), Cmax)
timeFrame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
measure: Ctrough: Trough Observed Plasma Concentration
timeFrame: Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose)
measure: Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178
timeFrame: Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)
measure: Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab
timeFrame: Cycle 1-6 timepoints can include (Pre-dose, 336, 696 hours post dose)
measure: Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.
timeFrame: Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)
measure: The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8
timeFrame: Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)
measure: Tumor Pharmacodynamics of BMS-986178 in Combination With Nivolumab or Nivolumab Monotherapy in Part 8
timeFrame: Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 hours post dose)
measure: The Number of Participants With Sustained T Cell Expansion With DPV-001 in Combination With Nivolumab or Nivolumab Monotherapy in Part 9
timeFrame: Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University Of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University Medical Center (Cumc)
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Ramat Gan
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Milano
country: Italy
facility: IRCCS Istituto Nazionale Tumori Milano
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Utrecht
country: Netherlands
facility: Local Institution
city: Barcelona
country: Spain
facility: H. Univ. Vall dHebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Majadahonda - Madrid
country: Spain
facility: Hosp. Univ. Puerta De Hierro
city: Malaga
country: Spain
facility: Hospital Universitario Virgen De La Victoria
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Gutierrez M, Moreno V, Heinhuis KM, Olszanski AJ, Spreafico A, Ong M, Chu Q, Carvajal RD, Trigo J, Ochoa de Olza M, Provencio M, De Vos FY, De Braud F, Leong S, Lathers D, Wang R, Ravindran P, Feng Y, Aanur P, Melero I. OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Clin Cancer Res. 2021 Jan 15;27(2):460-472. doi: 10.1158/1078-0432.CCR-20-1830. Epub 2020 Nov 4.