A Safety Study of Lirilumab in Combination With Nivolumab or in Combination With Nivolumab and Ipilimumab in Advanced and/or Metastatic Solid Tumors

A Phase 1 Study of the Safety and Pharmacokinetics of Anti-KIR Monoclonal Antibody (Lirilumab, BMS-986015) in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab,BMS-936558) or in Combination With Nivolumab and Anti-CTLA-4 Monoclonal Antibody (Ipilimumab, BMS-734016) in Advanced and/or Metastatic Solid Tumors

The purpose of this study is to determine whether lirilumab in combination with nivolumab or in combination with nivolumab and ipilimumab is safe in the treatment of advanced and/or metastatic solid tumors

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: Ipilimumab; Biological: Lirilumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 2778577
      • Local Institution
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 6500017
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

• Participants must have histologic or cytologic confirmation of a solid malignancy that is advanced (metastatic and/or unresectable)
• Presence of at least 1 lesion with measurable disease as defined by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria for response assessment
• The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Participants with untreated central nervous system (CNS) metastases
• Participants with an active, known, or suspected autoimmune disease
• Uncontrolled or significant cardiovascular disease

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part One Combination Therapy; Lirilumab and Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Lirilumab; Specified dose on specified days; Other Names: BMS-986015
Experimental: Part 2 Combination Therapy; Lirilumab, Nivolumab and Ipilimumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: Ipilimumab; Specified dose on specified days; Other Names: BMS-734016; Yervoy; Biological: Lirilumab; Specified dose on specified days; Other Names: BMS-986015

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years
Incidence of adverse events (AEs)	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years
Incidence of serious adverse events (SAEs)	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years
Incidence of death	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years
Frequency of laboratory test toxicity grade shifting from baseline	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years
Incidence of AEs leading to discontinuation	To assess the safety and tolerability of lirilumab in combination with nivolumab	Up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Incidence of adverse events (AEs)	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Incidence of serious adverse events (SAEs)	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Incidence of death	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Frequency of laboratory test toxicity grade shifting from baseline	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Maximum serum observed concentration (Cmax)	To characterize the Pharmacokinetic (PK) of lirilumab given in combination with nivolumab	Up to two years
Time of maximum observed serum concentration (Tmax)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration [AUC(0-T)]	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)]	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Trough observed serum concentration (Ctrough)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Area under the serum concentration-time curve in one dosing interval [AUC(TAU)]	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Clearance (CL)	To characterize the PK and immunogenicity of lirilumab given in combination with nivolumab	Up to two years
Volume of distribution at steady state (Vss)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Ratio of an exposure measure at steady-state to that after the first dose (AI)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Half-life (T-HALF)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (T-HALF eff)	To characterize the PK of lirilumab given in combination with nivolumab	Up to two years
Best overall response (BOR)	To assess the preliminary anti-tumor activity	Up to two years
Duration of response (DOR)	To assess the preliminary anti-tumor activity	Up to two years
Incidence of anti-drug antibody (ADA)	To characterize immunogenicity	Up to two years
Incidence of AEs leading to discontinuation	To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab	Up to two years
Maximum serum observed concentration (Cmax)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Time of maximum observed serum concentration (Tmax)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration [AUC(0-T)]	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)]	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Trough observed serum concentration (Ctrough)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Area under the serum concentration-time curve in one dosing interval [AUC(TAU)]	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Clearance (CL)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Volume of distribution at steady state (Vss)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Ratio of an exposure measure at steady-state to that after the first dose (AI)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Half-life (T-HALF)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years
Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (T-HALF eff)	To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab	Up to two years

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

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): July 14, 2017
• Primary Completion (Actual): August 6, 2020
• Study Completion (Actual): August 6, 2020

Study Registration Dates

• First Submitted: June 28, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): June 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

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; Ipilimumab
• Other Study ID Numbers: CA223-030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes