Study to evaluate the safety of Anti-LAG-3 alone or in combination with Nivolumab in the treatment of solid tumors.

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

ICTRP Trial ID
NCT01968109 (ICTRP)

Official title (approved by ethics committee)
A Phase 1/2a 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 (BASEC)

Academic 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 (ICTRP)

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 (ICTRP)

Disease under investigation
Neoplasms by Site (ICTRP)

Intervention under investigation
Biological: RelatlimabBiological: NivolumabBiological: BMS-986213 (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
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 (ICTRP)

not available

Primary and secondary end points
Proportion of participants with Adverse Events (AEs);Proportion of participants with Serious Adverse Events (SAEs);Proportion of Deaths;Proportion of participants with laboratory abnormalities in blood;Proportion of participants with laboratory abnormalities in blood serum;Proportion of participants with laboratory abnormalities in urine;Objective response rate (ORR);Disease control rate (DCR);Duration of response (DOR);Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ;Proportion of participants with AEs leading to discontinuation of treatment (ICTRP)

Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab;Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab;Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab;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;Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab;Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab;Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab;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;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;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;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;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;Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab;Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab;QTc interval from centrally read electrocardiograms (ECGs);Best overall response (BOR);ORR;DCR;Duration of response (DOR);Progression-free survival (PFS) rates;Overall survival (OS);Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Bristol-Myers Squibb, Bristol-Myers Squibb (ICTRP)

Secondary trial IDs
2023-508067-70, CA224-020 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT01968109 (ICTRP)