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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01968109




Registration number
NCT01968109
Ethics application status
Date submitted
25/09/2013
Date registered
23/10/2013
Date last updated
5/05/2020

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2014-002605-38
Secondary ID [2] 0 0
CA224-020
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms by Site 0 0
Condition category
Condition code
Cancer 0 0 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Relatlimab
Other interventions - Nivolumab
Other interventions - BMS-986213

Experimental: Relatlimab - Relatlimab (BMS-986016) specified dose on specified days

Experimental: Relatlimab + Nivolumab - Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days

Experimental: BMS-986213 - Relatlimab (BMS-986016) + Nivolumab (BMS-936558)


Other interventions: Relatlimab


Other interventions: Nivolumab


Other interventions: BMS-986213
Relatlimab + Nivolumab

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of participants with Adverse Events (AEs) - Grade 3 or higher per CTCAE v4 (Common Terminology Criteria for Adverse Events)
Timepoint [1] 0 0
Approximately Up to 3 years
Primary outcome [2] 0 0
Proportion of participants with Serious Adverse Events (SAEs) - Grade 3 or higher per CTCAE v4 ( Common Terminology Criteria for Adverse Events)
Timepoint [2] 0 0
Approximately Up to 3 years
Primary outcome [3] 0 0
Proportion of Deaths
Timepoint [3] 0 0
Approximately Up to 3 years
Primary outcome [4] 0 0
Proportion of participants with laboratory abnormalities in blood
Timepoint [4] 0 0
Approximately Up to 3 years
Primary outcome [5] 0 0
Proportion of participants with laboratory abnormalities in blood serum
Timepoint [5] 0 0
Approximately Up to 3 years
Primary outcome [6] 0 0
Proportion of participants with laboratory abnormalities in urine
Timepoint [6] 0 0
Approximately Up to 3 years
Primary outcome [7] 0 0
Objective response rate (ORR)
Timepoint [7] 0 0
Approximately 3 years
Primary outcome [8] 0 0
Disease control rate (DCR)
Timepoint [8] 0 0
Approximately 3 years
Primary outcome [9] 0 0
Duration of response (DOR)
Timepoint [9] 0 0
Approximately 3 years
Primary outcome [10] 0 0
Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ
Timepoint [10] 0 0
Approximately 3 years
Primary outcome [11] 0 0
Proportion of participants with AEs leading to discontinuation of treatment
Timepoint [11] 0 0
Approximately up to 3 years
Secondary outcome [1] 0 0
Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [1] 0 0
Approximately 2.3 years
Secondary outcome [2] 0 0
Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [2] 0 0
Approximately 2.3 years
Secondary outcome [3] 0 0
Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [3] 0 0
Approximately 2.3 years
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Approximately 2.3 years
Secondary outcome [5] 0 0
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [5] 0 0
Approximately 2.3 years
Secondary outcome [6] 0 0
Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [6] 0 0
Approximately 2.3 years
Secondary outcome [7] 0 0
Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [7] 0 0
Approximately 2.3 years
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Approximately 2.3 years
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Approximately 2.3 years
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Approximately 2.3 years
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Approximately 2.3 years
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Approximately 2.3 years
Secondary outcome [13] 0 0
Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab
Timepoint [13] 0 0
Approximately 2.3 years
Secondary outcome [14] 0 0
Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab
Timepoint [14] 0 0
Approximately 2.3 years
Secondary outcome [15] 0 0
QTc interval from centrally read electrocardiograms (ECGs)
Timepoint [15] 0 0
Approximately 2.3 years
Secondary outcome [16] 0 0
Best overall response (BOR)
Timepoint [16] 0 0
Approximately 3 years
Secondary outcome [17] 0 0
ORR
Timepoint [17] 0 0
Approximately 3 years
Secondary outcome [18] 0 0
DCR
Timepoint [18] 0 0
Approximately 3 years
Secondary outcome [19] 0 0
Duration of response (DOR)
Timepoint [19] 0 0
Approximately 3 years
Secondary outcome [20] 0 0
Progression-free survival (PFS) rates
Timepoint [20] 0 0
Up to approximately 3 years
Secondary outcome [21] 0 0
Overall survival (OS)
Timepoint [21] 0 0
Approximately 2 years
Secondary outcome [22] 0 0
Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
Timepoint [22] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.



- 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)
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Gallipoli Medical Research Foundation - Greenslopes
Recruitment hospital [3] 0 0
Tasman Oncology Research Pty Ltd - Southport
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Austria
State/province [15] 0 0
Wien
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Denmark
State/province [18] 0 0
Copenhagen
Country [19] 0 0
Denmark
State/province [19] 0 0
Herlev
Country [20] 0 0
Finland
State/province [20] 0 0
Helsinki
Country [21] 0 0
France
State/province [21] 0 0
Marseille Cedex 5
Country [22] 0 0
France
State/province [22] 0 0
Nantes Cedex 01
Country [23] 0 0
France
State/province [23] 0 0
Pierre Benite Cedex
Country [24] 0 0
France
State/province [24] 0 0
Toulouse Cedex 9
Country [25] 0 0
France
State/province [25] 0 0
Villejuif
Country [26] 0 0
Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Heilbronn
Country [28] 0 0
Germany
State/province [28] 0 0
Wuerzburg
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Padova
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Hokkaido
Country [34] 0 0
Japan
State/province [34] 0 0
Shizuoka
Country [35] 0 0
Japan
State/province [35] 0 0
Tokyo
Country [36] 0 0
Netherlands
State/province [36] 0 0
Amsterdam
Country [37] 0 0
Norway
State/province [37] 0 0
Oslo
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Malaga
Country [40] 0 0
Spain
State/province [40] 0 0
Pamplona
Country [41] 0 0
Switzerland
State/province [41] 0 0
Lausanne
Country [42] 0 0
Switzerland
State/province [42] 0 0
Zurich
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Greater London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT01968109
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email:
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Clinical.Trials@bms.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01968109