An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

Neoplasms by Site Clinical Trial

Official title:

A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01968109
• Other study ID #: CA224-020
• Secondary ID: 2023-508067-70
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 5, 2013
• Est. completion date: September 10, 2024

Study information

• Verified date: March 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the safety, tolerability and effectiveness of experimental medication BMS-986016 administered alone and in combination with nivolumab in patients with solid tumors that have spread and/or cannot be removed by surgery. The following tumor types are included in this study: Non-Small Cell Lung Cancer (NSCLC), gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma, that have NOT previously been treated with immunotherapy. NSCLC and melanoma that HAVE previously been treated with immunotherapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1499
• Est. completion date: September 10, 2024
• Est. primary completion date: September 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
• For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
• Progressed, or been intolerant to, at least one standard treatment regimen, except for participants in 1st line cohorts.
• ECOG performance status between 0 and 2
• At least 1 lesion with measurable disease at baseline
• Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)

Exclusion Criteria:

• Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
• Autoimmune disease
• Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• Uncontrolled CNS metastases Other protocol defined inclusion/exclusion criteria could apply

Related Conditions & MeSH terms

• Neoplasms by Site

Intervention

Biological:
• Relatlimab

• Nivolumab

• BMS-986213
Relatlimab + Nivolumab

Locations

Country	Name	City	State
Australia	Local Institution - 0031	Brisbane	Queensland
Australia	Local Institution - 0033	Melbourne	Victoria
Australia	Local Institution - 0032	Nedlands	Western Australia
Australia	Local Institution - 0029	North Sydney	New South Wales
Australia	Local Institution - 0039	Southport	Queensland
Austria	Local Institution - 0023	Wien
Austria	Local Institution - 0024	Wien
Canada	Local Institution - 0050	Quebec City	Quebec
Canada	Local Institution - 0049	Toronto	Ontario
Denmark	Local Institution - 0028	Copenhagen
Denmark	Local Institution - 0020	Herlev
Finland	Local Institution - 0021	Helsinki	Uusimaa
France	Local Institution - 0038	Marseille Cedex 5
France	Local Institution - 0037	Nantes Cedex 01
France	Local Institution - 0036	Pierre Benite Cedex
France	Local Institution - 0026	Toulouse Cedex 9
France	Local Institution - 0018	Villejuif
Germany	Local Institution - 0007	Essen
Germany	Local Institution - 0040	Heilbronn
Germany	Local Institution - 0041	Wuerzburg
Italy	Local Institution - 0014	Milano
Italy	Local Institution - 0013	Napoli
Italy	Local Institution - 0035	Padova
Japan	Local Institution - 0052	Chuo-ku	Tokyo
Japan	Local Institution - 0055	Nagoya-shi	Aichi
Japan	Local Institution - 0059	Sapporo-shi	Hokkaido
Japan	Local Institution - 0054	Sunto-gun	Shizuoka
Netherlands	Local Institution - 0025	Amsterdam
Norway	Local Institution - 0019	Oslo
Spain	Local Institution - 0015	Barcelona
Spain	Local Institution - 0046	Malaga
Spain	Local Institution - 0006	Pamplona
Switzerland	Local Institution - 0017	Lausanne
Switzerland	Local Institution - 0016	Zuerich
United Kingdom	Local Institution - 0022	London	Greater London
United Kingdom	Local Institution - 0027	London	Greater London
United Kingdom	Local Institution - 0034	Manchester
United States	Local Institution - 0047	Allentown	Pennsylvania
United States	Local Institution - 0053	Aurora	Colorado
United States	Local Institution - 0004	Baltimore	Maryland
United States	Local Institution - 0001	Boston	Massachusetts
United States	Local Institution - 0003	Chicago	Illinois
United States	Local Institution - 0057	Dallas	Texas
United States	Local Institution - 0011	Detroit	Michigan
United States	Local Institution - 0045	Houston	Texas
United States	Local Institution - 0043	La Jolla	California
United States	Local Institution - 0005	New York	New York
United States	Local Institution - 0048	Niles	Illinois
United States	Local Institution - 0010	Pittsburgh	Pennsylvania
United States	Local Institution - 0002	Portland	Oregon
United States	Local Institution - 0051	Rochester	Minnesota
United States	Local Institution - 0044	Saint Louis	Missouri
United States	Local Institution - 0008	Seattle	Washington
United States	Local Institution - 0058	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  Finland,  France,  Germany,  Italy,  Japan,  Netherlands,  Norway,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with Adverse Events (AEs)	Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)	Approximately Up to 3 years
Primary	Proportion of participants with Serious Adverse Events (SAEs)	Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)	Approximately Up to 3 years
Primary	Proportion of Deaths		Approximately Up to 3 years
Primary	Proportion of participants with laboratory abnormalities in blood		Approximately Up to 3 years
Primary	Proportion of participants with laboratory abnormalities in blood serum		Approximately Up to 3 years
Primary	Proportion of participants with laboratory abnormalities in urine		Approximately Up to 3 years
Primary	Objective response rate (ORR)		Approximately 3 years
Primary	Disease control rate (DCR)		Approximately 3 years
Primary	Duration of response (DOR)		Approximately 3 years
Primary	Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ		Approximately 3 years
Primary	Proportion of participants with AEs leading to discontinuation of treatment		Approximately up to 3 years
Secondary	Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Effective elimination half-life that explains the degree of area under the concentration-time curve (AUC) accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Accumulation index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab		Approximately 2.3 years
Secondary	Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab		Approximately 2.3 years
Secondary	QTc interval from centrally read electrocardiograms (ECGs)		Approximately 2.3 years
Secondary	Best overall response (BOR)		Approximately 3 years
Secondary	ORR		Approximately 3 years
Secondary	DCR		Approximately 3 years
Secondary	Duration of response (DOR)		Approximately 3 years
Secondary	Progression-free survival (PFS) rates		Up to approximately 3 years
Secondary	Overall survival (OS)		Approximately 2 years
Secondary	Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ		Approximately 3 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting