An Investigational Immuno-therapy Study of Experimental Medication BMS-986179 Given Alone and in Combination With Nivolumab

A Phase 1/2a Study of BMS-986179 Administered Alone and in Combination With Nivolumab (BMS-936558) in Subjects With Advanced Solid Tumors

The purpose of this study is to assess the safety and tumor-shrinking ability of experimental medication BMS-986179 alone and when combined with Nivolumab, in patients with solid cancers that are advanced or have spread.

Study Overview

• Status: Completed
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Biological: Nivolumab; Biological: BMS-986179; Biological: rHuPH20

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Local Institution - 0019
    • Sydney, New South Wales, Australia, 2010
      • Local Institution - 0017
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 0018
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution - 0003
    • Toronto, Ontario, Canada, M5G 1Z5
      • Local Institution - 0002
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Local Institution - 0024
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 0014
• France
  • Marseille, France, 13273
    • Local Institution - 0033
  • Marseille Cedex 5, France, 13385
    • Local Institution - 0021
  • Toulouse Cedex 9, France, 31059
    • Local Institution - 0008
  • Villejuif Cedex, France, 94805
    • Local Institution - 0007
• Germany
  • Freiburg, Germany, 79106
    • Local Institution - 0016
  • Munich, Germany, 81675
    • Local Institution - 0015
• Italy
  • Napoli, Italy, 80131
    • Local Institution - 0012
  • Padova, Italy, Padova
    • Local Institution - 0013
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0006
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 0028
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0001
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Local Institution - 0022
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 0023
    • New York, New York, United States, 10032
      • Local Institution - 0005
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 0020
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0004
  • Texas
    • Dallas, Texas, United States, 75230
      • Local Institution - 0009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Inclusion Criteria:

• Solid cancers that are advanced or have spread (for which alternative therapies were deemed not effective)
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Acceptable lab testing results
• Allow biopsies

Exclusion Criteria:

• Central nervous system (CNS) tumors
• Uncontrolled or significant cardiovascular diseases
• Active or known autoimmune disease
• Organ transplant

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A-Monotherapy; BMS-986179, dose as specified	Biological: BMS-986179; Specified dose on specified days
Experimental: Arm B- Combination Therapy; BMS-986179 + nivolumab, dose as specified	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BMS-986179; Specified dose on specified days
Experimental: Arm C-Combination Therapy; BMS-986179 + rHuPH20, dose as specified	Biological: BMS-986179; Specified dose on specified days; Biological: rHuPH20; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Drug Related AEs, SAEs, AEs Leading to Discontinuation and Deaths.	Number of participants with drug related adverse events (AE), drug related serious adverse events (SAE), drug related AEs Leading to discontinuation and drug related deaths	From first dose to 100 days post last dose: Part 1 up to 25.1 months, Part 2 SC up to 17.5 months, RCC Mono up to 28.1 months, Part 2 up to 27.2 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Best Overall Response (BOR) at Week 24	Best overall response (BOR) is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.	from initial treatment to week 24
Percentage of Participants With an Objective Response Rate (ORR) at Week 24	ORR is defined as the percentage of all treated participants whose BOR is either a CR or PR.	from initial treatment to week 24
Progression Free Survival Rate (PFSR) at Week 24	PFSR at 24 weeks is defined as the percentage of treated participants remaining progression free and surviving at 24 weeks.	from initial treatment to week 24
Median Duration of Response (DOR)	DOR (computed for all treated subjects with a BOR of CR or PR) is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first.	from first measure response approximately up to 25 months
Cmax	Cmax is defined as maximum plasma concentration of the drug	Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days
Tmax	Tmax is defined is the time to maximum plasma concentration	Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days
AUC (0-T)	Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration	Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days
AUC (Tau)	Area under the plasma concentration time-curve. AUC over the dosing interval.	Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days
Ctau	Ctau is defined as the concentration of study drug at the end of the dosing interval	Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days
Mean Change From Baseline in CD73 Assays	Mean change from baseline in CD73 assays at the end of Part 1A treatment period Assays Measured: EHC CD73 H-score IHC CD73 Cytoplasm H-Score IHC CDS73 Membrane H-Score The H-score is given by the ratio of the weighted sum of the number of positive cells to the total number of detected cells. The H-score captures both the intensity and the proportion of the biomarker of interest from the IHC image and comprises values between 0 and 300. The lower the number equals a better prognosis.	approximately up to 95 weeks
Number of Participants With a Positive Anti-drug Antibody (ADA) Test.	A participant with at least one ADA-positive sample relative to baseline at any time after initiation of treatment with BMS-986179 and nivolumab.	From first dose to last dose: Part 1: up to 95 weeks, Part 2 SC: up to 62 weeks, RCC Mono: up to 108 weeks, Part 2: up to 104 weeks

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2016
• Primary Completion (Actual): October 12, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA013-004; 2016-000603-91 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No