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Completed

NCT Number: NCT01968109

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

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.

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Key information

Conditions

Neoplasms by Site Neoplasms

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Local Institution - 0029, North Sydney, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Relatlimab

Biological

Other names: BMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)

Nivolumab

Biological

Other names: Anti-PD-1 (Anti-Programmed-Death-1), BMS-936558

BMS-986213

Biological

Relatlimab + Nivolumab

Primary outcomes

  1. Number of Participants With Adverse Events, Deaths and Clinically Relevant Laboratory Abnormalities

    Time frame: From first dose and within 135 days after last dose of study therapy (Up to approximately 82 months)

    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect.

  2. Part C, D1, D2, E - Objective Response Rate Per BICR

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  3. Part C, D1, D2, E - Disease Control Rate (DCR) Per BICR

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  4. Part C, D1, D2, E - Duration of Response (DOR) Per BICR

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  5. Part D1: Number of Participants With Adverse Events in the Broad Scope Standardized MedDRA (SMQ) Anaphylactic Reaction Occurring Within 2 Days of Any Doses of Study Therapy

    Time frame: From first dose and within 2 days of first dose of study therapy

    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

  6. Part C, D1, D2, E - Objective Response Rate Per BICR

    Time frame: From first dose (Day 1) and up to 97 months

    ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Secondary outcomes

  1. Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per BICR

    Time frame: Up to 12 months

    Progression Free Survival Rates at 12 months is defined as the proportion of participants who achieve PFS at 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  2. Part D1 and D2: Overall Survival (OS) at 12 and 24 Months

    Time frame: At 12 and 24 months after first dose

    Overall survival at 1 year, and 2 years is defined as the proportion of participants who are alive at 1 year, and 2 years. Based on Kaplan-Meier Estimates.

  3. Part C, D1, D2, E - Objective Response Rate Per Investigator

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  4. Part C, D1, D2, E - Disease Control Rate (DCR) Per Investigator

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  5. Part C, D1, D2, E - Duration of Response (DOR) Per Investigator

    Time frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)

    DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  6. Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per Investigator

    Time frame: Up to 12 months

    Progression Free Survival Rates up to 12 months is defined as the proportion of participants who achieve PFS up to 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  7. Number of Participants With Positive Anti Drug Antibodies

    Time frame: predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)

    Blood samples were collected to assess anti-drug antibodies.

  8. Part A, A/A1, and B: Number of Participants With Clinically Relevant QT Prolongation

    Time frame: predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days)

    Abnormal electrocardiogram parameter included QT prolongation.

  9. Maximum Observed Concentration (Cmax) of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 1 and 3

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

  10. Time to Maximum Observed Concentration (Tmax) of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

  11. Area Under the Concentration-time Curve in One Dosing Interval (AUCtau) of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab).

  12. Part A/A1, B, C, D1, D2 and E: Trough Observed Concentration (Ctrough) of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days)

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). Ctrough is defined as the lowest concentration of drug in the blood immediately before the next dose is administered. Ctrough was only assessed for arm Part A/A1, B, C, D1, D2 and E as pre-specified.

  13. Part A/A1, B, CTotal Body Clearance (CLT) of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days).

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). CLT was only assessed for arm Part A/A1, B, C as pre-specified.

  14. Part A/A1, B, C AUC Accumulation Index AI_AUC of BMS-986016 (Relatlimab)

    Time frame: Day 1 of Cycle 3 (Each cycle consist of 28 days)

    Blood samples were collected for assessment of pharmacokinetic parameter of BMS-986016 (relatlimab). AUC Accumulation Index is a pharmacokinetic metric used to quantify how much a drug accumulates in the body after repeated dosing compared to a single dose. It is ratio of AUC Steady State (AUCss) and AUC1. AUCₛₛ is the area under the plasma concentration-time curve during a dosing interval at steady state (after repeated doses). AUC₁ is the area under the curve after a single dose. Only assessed for arm Part A/A1, B, C as pre-specified.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2024
Study completion
2025
First posted
Oct 23, 2013
Registry last updated
Apr 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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