An Investigational Immuno-Therapy Study of Experimental Medication BMS-986242 Given in Combination With Nivolumab in Patients With Advanced Cancer

A Phase 1/2a Study of BMS-986242 Administered in Combination With Nivolumab (BMS-936558, Anti-PD-1) in Advanced Malignant Tumors

The purpose of this study is to investigate safety of experimental medication BMS-986242 and Nivolumab in patients with advanced cancers.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: BMS-986242

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Hoag Memorial Hospital Presbyterian
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution

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:

• Histologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1
• Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Ability to swallow tablets
• Adequate bone marrow and organ function, as defined by the protocol

Exclusion Criteria:

• Participants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll)
• Ocular melanoma
• Any significant acute or chronic medical illness
• Prior malignancy
• Other active malignancy requiring concurrent intervention
• Prior organ allograft or allogeneic bone marrow transplantation
• Participants with active, known, or suspected autoimmune disease
• Requirement for daily supplemental oxygen
• Uncontrolled or significant cardiovascular disease
• Pre-existing liver disease
• Gastrointestinal disease known to interfere with absorption

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: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; BMS-986242 administered in combination with Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Anti-PD-1; Drug: BMS-986242; Specified dose on specified days
Experimental: Dose Expansion; BMS-986242 administered in combination with Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Anti-PD-1; Drug: BMS-986242; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE)	The primary objective to establish safety to be measured by the primary endpoint of AEs	From initiation of study treatment until 100 days after discontinuation of study treatment
Number of Participants With Serious Adverse Events (SAE)	The primary objective to establish safety to be measured by the primary endpoint of SAEs	From the date of participant's written consent until 100 days after discontinuation of nivolumab or participation in the study
Number of Participants With Dose Limiting Toxicities (DLT)	The primary objective to establish safety to be measured by the primary endpoint of dose limiting toxicities	Approximately 2 years
Number of Participants With AEs Leading to Discontinuation	The primary objective to establish safety to be measured by the primary endpoint of AEs leading to discontinuation	Approximately 2 years
Number of Deaths	The primary objective to establish safety to be measured by the primary endpoint of deaths	Approximately 2 years
Number of Participants With Laboratory Abnormalities	The primary objective to establish safety to be measured by the primary endpoint of clinical laboratory test abnormalities	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Time of Maximum Observed Plasma Concentration (Tmax)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Area Under the Concentration-time Curve From Time Zero to Infinity [AUC(INF)]	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Trough Observed Plasma Concentration at the End of the Dosing Interval (Ctrough)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Apparent Elimination Half-life (T-HALF)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Apparent Total Body Clearance (CLT/F)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Apparent Volume of Distribution at Steady State (Vss/F)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Accumulation Index (AI)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0. Accumulation index, calculated based on ratio of area under the curve (AUC) and Cmax at steady state to after the first dose.	Approximately 2 years
Percent Urinary Recovery Over 24 Hours (%UR24)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Percent Urinary Recovery Over 72 Hours (%UR72)	The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0	Approximately 2 years
Incidence of Anti-drug Antibody (ADA) to Nivolumab in Combination With BMS-986242	Baseline ADA-positive participant is defined as a participant who has a ADA detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment.	Approximately 2 years
Overall Response Rate (ORR)	ORR in participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors	Approximately 2 years

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): November 27, 2017
• Primary Completion (Actual): August 28, 2018
• Study Completion (Actual): August 28, 2018

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): August 26, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

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: CA024-001; 2017-003603-21 (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