An Investigational Immuno-therapy Study of Experimental Medication BMS-986156, Given by Itself or in Combination With Nivolumab in Patients With Solid Cancers or Cancers That Have Spread.

A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination With Nivolumab (BMS-936558, Anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tumor-shrinking ability of experimental medication BMS-986156, when given by itself or in combination with nivolumab in patients with solid cancers that are advanced or cancers that have spread.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Nivolumab; Drug: BMS-986156

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Cancer Therapy Center
    • Westmead, New South Wales, Australia, 2145
      • Local Institution
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Ltd
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0012
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Local Institution
• France
  • Paris Cedex 5, France, 75248
    • Local Institution
  • Toulouse Cedex 9, France, 31059
    • Institut Claudius Regaud
  • Vlllejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • Bonn, Germany, 53127
    • Local Institution
  • Freiburg, Germany, 79106
    • Local Institution
  • Wuerzburg, Germany, 97080
    • Local Institution
• Italy
  • Milano, Italy, 20133
    • Local Institution - 0014
  • Lombardia
    • Milan, Lombardia, Italy, 20141
      • Local Institution - 0015
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Local Institution
• Spain
  • Madrid, Spain, 28041
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
• Switzerland
  • St. Gallen, Switzerland, 9007
    • Cantonal Hospital St. Gallen
  • Zurich, Switzerland, 8091
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92093-0698
      • UCSD Moores Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic, P.C.

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 BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• For Dose Escalation:

  • Subjects with any previously treated advanced (metastatic or refractory) solid tumor

• For Cohort Expansion:

  • Subjects must have a previously treated advanced solid tumor to be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Willing and able to provide pre-treatment and on-treatment fresh tumor biopsy
• Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men

Exclusion Criteria:

• Known central nervous system metastases or central nervous system as the only source of disease
• Other concomitant malignancies (with some exceptions per protocol)
• Active, known or suspected autoimmune disease
• Uncontrolled or significant cardiovascular disease
• History of active or chronic hepatitis (e.g. Hep B or C)
• Impaired liver or bone marrow function
• Major surgery less than 1 month before start of the study

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-986156: Dose Escalation	Drug: BMS-986156
Experimental: BMS-986156 + nivolumab (nivo): Dose Escalation	Drug: Nivolumab; Drug: BMS-986156
Experimental: BMS-986156: Dose Expansion	Drug: BMS-986156
Experimental: BMS-986156 + nivolumab (nivo): Dose Expansion	Drug: Nivolumab; Drug: BMS-986156
Experimental: BMS986156 + Nivo: Cohort Expansion	Drug: Nivolumab; Drug: BMS-986156

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All Cause Adverse Events (AEs), Serious Adverse Events, AEs Leading to Discontinuation and Deaths	Number of participants with all cause adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, and number of participant deaths. AEs and laboratory values will be graded according to the NCI CTCAE version 4.03.	From first treatment to 100 days post last dose. Approximately 29 months
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests	Number of Participants with laboratory abnormalities in specific thyroid tests. TSH = Thyroid stimulating hormone ULN = Upper limit number LLN = Lower limit number	From first treatment to 100 days post last dose. Approximately 29 months
Number of Participants With Laboratory Abnormalities in Specific Liver Tests	Number of Participants with laboratory abnormalities in specific liver tests. ALT = alanine aminotransferase AST = aspartate aminotransferase ALP = alkaline phosphatase	From first treatment to 100 days post last dose. Approximately 29 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response	BOR will be defined by CR, PR, PD and SD 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	From first dose to a response or progressive disease (Approximately 50 Months)
Overall Response Rate	Defined as the percentage of all treated participants whose BOR is either a complete response(CR) or partial response(PR). 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.	From first dose to CR and PR (Approximately 50 Months)
Progression Free Survival (PFS)	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. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	From first dose to disease progression (Approximately 50 Months)
Duration of Response	All treated participants 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. 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.	From first dose to disease progression after a response (Approximately 50 Months)
Number of Participants With Anti-Drug Antibody Response	Number of participants with a positive Anti-Drug Antibody to BMS-986156 or nivolumab	At Cycle 3 Day 1; where each treatment cycle was 8 weeks

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Heinhuis KM, Carlino M, Joerger M, Di Nicola M, Meniawy T, Rottey S, Moreno V, Gazzah A, Delord JP, Paz-Ares L, Britschgi C, Schilder RJ, O'Byrne K, Curigliano G, Romano E, Patah P, Wang R, Liu Y, Bajaj G, Siu LL. Safety, Tolerability, and Potential Clinical Activity of a Glucocorticoid-Induced TNF Receptor-Related Protein Agonist Alone or in Combination With Nivolumab for Patients With Advanced Solid Tumors: A Phase 1/2a Dose-Escalation and Cohort-Expansion Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):100-107. doi: 10.1001/jamaoncol.2019.3848.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2015
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 6, 2015

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 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: CA009-002; 2015-002505-11 (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