Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Neoadjuvant relatlimab, BMS-986016, Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), Relatlimab (BMS-986016)
Relatlimab · 11 trials · 8 indications
The primary endpoint is the pathological response rate at surgery (between days 43 and 56) from the first dose of neoadjuvant study treatment. The pathological response is categorised thus: * Complete pathological response (pCR) - 0% viable tumour cells in the surgical specimen * Near complete pathological response - (near pCR) - \<10% viable tumour * Partial pathological response (pPR) - 10%-50% viable tumour * No pathological response (pNR) - \>50% viable tumour The proportion of participants with a pCR, or near pCR will determine the pathological response rate.
1. Proportion of patients enrolled in the study from the population of patients presenting to the clinic with new stage II disease, and the reason(s) for exclusion. 2. The proportion of stage II patients with residual disease following diagnostic biopsy. 3. Proportion of eligible patients who consent to the study. 4. The number of patients recruited per month compared to the expected 20 patients over 24 months or 0.84 per month.
PEPQ included 7 items 1. Pain or Discomfort (rated on 1 to 10 scale), 2. Length of time related to administration 3. Length of time related to administration impact amount of time to speak to doctor or nurse about illness or concern 4. Length of time for administration impact time to interact or socialize with other individuals 5. Convenience 6. Satisfaction 7. Choice of which route of administration would be preferred. 95% CI exact confidence interval was reported.
Percent Lymphocyte-activation gene 3 (LAG3) level (cell surface molecule expressed on activated T cells) expression from scRNAseq
Percent PD1 (programmed cell death protein 1) expression after completion of lead-in phase.
Percentage change in tumor size assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: * 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; see Appendix II on imaging guidance). * 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable). * 20 mm by chest X-ray.
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Percent of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Progression Free Survival (PFS) is defined as the time between the date of randomization and the date of first documented tumor progression, assessed by a blinded independent central review (BICR) (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death.
Bevacizumab DLTs: Include any AE causing \>42-day delay, GI perforation, nephrotic syndrome, Grade 3/4 infusion reactions, Death events, neutropenic fever, most non-hematologic toxicities (with specified exceptions), prolonged severe GI/electrolyte issues, significant fatigue, severe liver enzyme elevation, PRES/RPLS, severe hypertension or cardiac events, thromboembolism, major bleeding, wound complications, fistula, necrotizing fasciitis, and severe hematologic toxicity. Immunotherapy DLTs: Include severe immune-related events (eg, colitis, pneumonitis, uveitis), Grade 4 organ toxicities, serious hypersensitivity, prolonged/recurrent AEs, severe electrolyte/GI/fatigue events, Grade 5 events, severe hematologic, hepatic, neurologic, cardiac (myocarditis), and severe dermatologic reactions (eg, SJS/TEN, DRESS).
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 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.
Objective response rate (ORR) is defined as the percentage of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), 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.
Laboratory test results are graded using the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. Grade 3 = Severe or medically significant but not immediately life-threatening. Grade 4 = Life-threatening or disabling.
Adverse events are any unfavorable or unintended signs, symptoms, or diseases occurring in study participants during a clinical trial, regardless of whether they are related to the intervention. They include all-cause mortality, serious adverse events, and other events exceeding a set frequency threshold. Serious adverse events are a subset that result in significant outcomes such as death, life-threatening conditions, hospitalization or its prolongation, persistent or significant disability/incapacity, or other medically important conditions.
Objective Response Rate (ORR) is the percentage of participants whose best overall response is Complete Response (CR) or Partial Response (PR) per RECIST v1.1. CR is the disappearance of all target lesions and reduction of pathological lymph nodes to \<10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions from baseline. ORR is calculated as: (Number of participants with CR or PR ÷ Total participants) × 100. Confidence intervals are typically estimated using the Clopper-Pearson method.
Disease Control Rate (DCR) is the percentage of participants whose Best Overall Response (BOR) is Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1. CR is the disappearance of all target lesions and reduction of any pathological lymph nodes to \<10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions from baseline. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum diameters while on study. DCR is calculated as: (Number of participants with CR, PR, or SD ÷ Total participants) × 100.
Duration of Response (mDOR) is the median time from the first documented occurrence of Complete Response (CR) or Partial Response (PR) until disease progression or death, assessed per RECIST v1.1. CR is the disappearance of all target lesions and reduction of pathological lymph nodes to \<10 mm. PR is at least a 30% decrease in the sum of diameters of target lesions from baseline. Progression is defined as at least a 20% increase in the sum of diameters of target lesions or appearance of new lesions.
Number of participants with any grade adverse events (AEs), any grade serious adverse events (SAEs) and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. An 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.
Number of participants who died due to any cause.
Number of participants with laboratory abnormalities in specific hepatic tests based on SI unit convention. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * ALP \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Investigator-assessed ORR per International Working Group (IWG 2007) response criteria for malignant lymphoma is defined as the number of participants with a best overall documented response (BOR) of either a complete response (CR) or partial response (PR). Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir.
Investigator-assessed DoR per International Working Group (IWG 2007)) response criteria for malignant lymphoma is defined as the time between the date of first documented response (complete response or partial response) to the date of the first objectively documented progression, or death due to any cause, whichever occurs first. Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Neoadjuvant immunotherapy +/- Adjuvant immunotherapy | EXPERIMENTAL | NEOADJUVANT: All participants will receive neoadjuvant therapy with the fixed dose combination of intravenous relatlimab 160 mg and nivolumab 480 mg x 2 doses on days 1 and 29. SURGERY: All participants will have sentinel lymph node mapping and biopsy prior to a wide local excision of the primary melanoma between days 43 and 56. ADJUVANT: Participants with no pathological response or partial pathological response will receive the fixed dose combination of intravenous relatlimab 160 mg and nivolumab 480 mg for a further 11 doses. |
| Cohort 1: Metastatic Melanoma | EXPERIMENTAL | - |
| Cohort 2: Resected Melanoma | EXPERIMENTAL | - |
| Relatlimab | EXPERIMENTAL | Cycle 1: Relatlimab (BMS-986016) is supplied as a sterile 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV for the first 4 weeks (cycle 1). Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. |
| Nivolumab | EXPERIMENTAL | Cycle 1: Nivolumab (BMS-936558) is supplied as a sterile 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV for the first 4 weeks. Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks. |
| Relatlimab + Nivolumab | EXPERIMENTAL | Cycle 1+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV for the first 4 weeks (Cycle 1), then once every 4 weeks afterwards. |
| Arm A: Relatlimab + Nivolumab | EXPERIMENTAL | Combination |
| Arm B: Nivolumab | EXPERIMENTAL | Monotherapy |
| Cohort 1: Relatlimab Dose 1 + Nivolumab | EXPERIMENTAL | - |
| Cohort 2: Relatlimab Dose 2 + Nivolumab | EXPERIMENTAL | - |
| Arm A: Relatlimab + Nivolumab + Bevacizumab | EXPERIMENTAL | - |
| Arm B: Placebo + Nivolumab + Bevacizumab | EXPERIMENTAL | - |
| nivolumab + relatlimab + rHuPH20 | EXPERIMENTAL | - |
| Arm A | EXPERIMENTAL | Relatlimab + Nivolumab + BMS-986205 |
| Arm B | EXPERIMENTAL | Relatlimab + Nivolumab + Ipilimumab |
| Monotherapy | EXPERIMENTAL | Relatlimab (BMS-986016) administered every 2 weeks as a single agent intravenous formulation |
| Combination Therapy | EXPERIMENTAL | Relatlimab (BMS-986016) will be administered in combination with Nivolumab every 2 weeks or every 4 weeks as an intravenous formulation |
| Part A - relatlimab (Dose escalation) | EXPERIMENTAL | - |
| Part C - relatlimab + nivolumab (Dose escalation) | EXPERIMENTAL | - |
| Part B - relatlimab (Cohort expansion) | EXPERIMENTAL | - |
| Part D - relatlimab + nivolumab (Cohort expansion) | EXPERIMENTAL | - |
| BMS-986213 | EXPERIMENTAL | Relatlimab (BMS-986016) + Nivolumab (BMS-936558) |
| Name | Type | Description |
|---|---|---|
| Relatlimab and nivolumab fixed dose combination (FDC) | DRUG | Lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes, thus contributing to tumor-mediated T-cell exhaustion. The combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) results in increased T-cell activation compared to the activity of either antibody alone. |
| relatlimab+nivolumab | DRUG | Specified dose on specified days |
| relatlimab+nivolumab+rHuPH20 | DRUG | Specified dose on specified days |
| nivolumab | DRUG | Specified dose on specified days |
| nivolumab+rHuPH20 | DRUG | Specified dose on specified days |
| Relatlimab | DRUG | Relatlimab (BMS-986016) - 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV. |
| Relatlimab + Nivolumab | DRUG | Combination (Relatlimab + Nivolumab) therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV. |
| Bevacizumab | DRUG | Specified dose on specified days |
| Placebo | OTHER | Specified dose on specified days |
| rHuPH20 | DRUG | Specified dose on Specified days |
| BMS-986205 | DRUG | Specified dose on specified days |
| Ipilimumab | BIOLOGICAL | Specified dose on specified days |
| BMS-986016 | BIOLOGICAL | Specified Dose on Specified Days |
| BMS-936558 | BIOLOGICAL | Specified Dose on Specified Days |
| BMS-986213 | BIOLOGICAL | Relatlimab + Nivolumab |
Inclusion Criteria: 1. The patient (or legally acceptable representative, if applicable) provides written informed consent for the trial. 2. Male/female patients who are at least 18 years of age on the day of signing informed consent. 3. Histologically confirmed primary cutaneous melanoma from a pa...
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Relatlimab is an investigational monoclonal antibody being studied in oncology for advanced cancer, advanced solid tumors, melanoma, hepatocellular carcinoma, and hematologic neoplasms. It is being developed primarily in combination with nivolumab across these tumor types, including high risk clinical stage II cutaneous melanoma and advanced liver cancer.
Relatlimab targets LAG3, also known as lymphocyte activation gene 3. It is a LAG3 inhibitor monoclonal antibody. By binding LAG3, relatlimab is designed to block an inhibitory checkpoint receptor on immune cells, which is being studied as a way to support antitumor immune responses in combination with nivolumab.
Relatlimab is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is studying relatlimab both as a single agent and in fixed dose combination with nivolumab across multiple cancer indications.
Relatlimab is in Phase 1 clinical development. It is investigational and has not been approved. The Phase 1 program includes studies in Chinese participants with advanced solid tumors and in advanced liver cancer in combination with nivolumab and bevacizumab.
Relatlimab trials include NCT06101134, a Phase 2 study of subcutaneous versus intravenous nivolumab and nivolumab plus relatlimab in melanoma; NCT05498480, a completed Phase 1 study in Chinese participants with advanced solid tumors; NCT05418972, a Phase 2 neoadjuvant study in stage II melanoma; and NCT05337137, a completed Phase 1 study in advanced liver cancer.
Yes, BMS-986016 is an alternative name for relatlimab. The asset is also referred to as relatlimab plus nivolumab, relatlimab and nivolumab fixed dose combination (FDC), and neoadjuvant relatlimab, reflecting the combination regimens under study.