Melanoma
Conditions
Keywords
Nivolumab, Relatlimab, FDC, Melanoma, rHuPH20, OPDUALAG
Brief summary
The purpose of this study is to demonstrate that the study drug exposure level of the nivolumab + relatlimab FDC subcutaneous (SC) formulation is not worse than nivolumab + relatlimab FDC intravenous (IV) administration in participants with previously untreated metastatic or unresectable melanoma.
Interventions
Specified dose on specified days
DRUGrHuPH20
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Halozyme Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1/Lansky Performance Score ≥ 80% for adolescents (≥ 12 to \< 18 years of age). * Participants must have histologically confirmed Stage III (unresectable) or Stage IV (metastatic) melanoma, per the American Joint Committee for Cancer (AJCC) staging system. * Participants must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). * Participants must be ≥ 12 years of age. Participants who are ≥ 12 years of age and \< 18 years of age (adolescents) must weigh ≥ 40 kg at the time of signing the informed consent (assent). * Participants must have histologically confirmed Stage III (unresectable) or Stage IV (metastatic) melanoma, per the AJCC staging system (8th edition).
Exclusion criteria
* Participants must not have ocular melanoma. * Participants must not have a history of myocarditis, regardless of etiology. * Participants must not have a condition requiring systemic treatment with either corticosteroids (\>10 milligrams \[mg\] daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Time-Averaged Nivolumab Serum Concentration Over the First 28 Days (Cavgd28-Nivo) on Natural Logarithmic Scale | Pre-dose (Day 1 to Day 28) | Blood samples were collected to assess serum concentration. |
| Adjusted Time-Averaged Relatlimab Serum Concentration Over the First 28 Days (Cavgd28-Rela) on Natural Logarithmic Scale | Pre-dose (Day 1 to Day 28) | Blood samples were collected to assess serum concentration. |
| Adjusted Trough Nivolumab Serum Concentration at Steady-State (Cminss-Nivo) on Natural Logarithmic Scale | Pre-dose (Day 1 to Day 28) | Blood samples were collected to assess serum concentration. |
| Adjusted Trough Relatlimab Serum Concentration at Steady-State (Cminss-Rela) on Natural Logarithmic Scale | Pre-dose (Day 1 to Day 28) | Blood samples were collected to assess serum concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Per Investigator | 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 126 weeks) | Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). 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. |
| Objective Response Rate (ORR) by BICR | 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 126 weeks) | 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. |
| Disease Control Rate (ORR) Per BICR | 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 126 weeks) | Disease control rate (DCR) is defined as the percentage of participants who achieve a BOR of confirmed Complete Response (CR), confirmed Partial Response (PR), or stable disease (SD), based on BICR assessments (using RECIST 1.1) divided by the number of all randomized participants. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. |
| Time to Response (TTR) Per BICR | 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 126 weeks) | Time to response (TTR) assessed by BICR is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. 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. |
| Duration of Response (DoR) Per BICR | 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 126 weeks) | Duration of Response (DOR) in months is defined as the time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. CR is complete disappearance of all target lesions except nodal disease; all target nodes must decrease to normal size (short axis \< 10 mm). PR is ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. Disease progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. |
| Progression Free Survival Per BICR | 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 126 weeks) | Progression free survival (PFS) is defined as time from on treatment to disease progression or death (whichever comes first). 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. |
| Objective Response Rate (ORR) Per Investigator | 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 126 weeks) | 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 Investigator 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. |
| Disease Control Rate (ORR) Per Investigator | 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 126 weeks) | Disease control rate (DCR) is defined as the percentage of participants who achieve a BOR of confirmed Complete Response (CR), confirmed Partial Response (PR), or stable disease (SD), based on Investigator assessments (using RECIST 1.1) divided by the number of all randomized participants. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. |
| Time to Response (TTR) Per Investigator | 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 126 weeks) | Time to response (TTR) assessed by Investigator is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. 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. |
| Duration of Response (DoR) Per Investigator | 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 126 weeks) | Duration of Response (DOR) in months is defined as the time from date of the first documentation of objective response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. CR is complete disappearance of all target lesions except nodal disease; all target nodes must decrease to normal size (short axis \< 10 mm). PR is ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. Disease progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. |
| Overall Survival (OS) | 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 126 weeks) | Overall survival is defined as the time from the first dosing date (or from randomization/on treatment) to the date of death from any cause. Median computed using Kaplan-Meier method. |
| Number of Participants With Adverse Events, SAEs, AEs Leading to Discontinuation and Deaths | First dose (Day 1) and 30 days after last dose of study therapy (up to approximately 26 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence at any dose that: results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, results in a congenital abnormality or birth defect, or is an important medical event that may not result in death, be life-threatening, or require hospitalization, but may require medical or surgical intervention to prevent any of the outcomes listed above. |
| Number of Participants With Immune-mediate Adverse Events (IMAEs) | First dose (Day 1) and 135 days after last dose of study therapy (up to approximately 29 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants With Other Event of Special Interest (OESI) | First dose (Day 1) and 100 days after last dose of study therapy (up to approximately 28 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants With On-Treatment Worst CTCAE Grade 3-4 Laboratory Parameters | First dose (Day 1) and 30 days after last dose of study therapy (up to approximately 26 months) | AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. |
| Trough Serum Concentration of Nivolumab and Relatlimab (Cmind28) at Day 28 | Pre-dose at Day 28 | Blood samples were collected to assess serum concentration. |
| Change From Baseline Functional Assessment of Cancer Therapy -Melanoma (FACT-M) Total Score | Baseline (Day 1) and Week 85 | The FACT-M questionnaire was used to assess the effects of disease symptoms on functioning and well-being. As a generic cancer-related core, the FACT-M includes the 27-item FACT General (FACT-G) to assess physical well-being (PWB; 7 items), social/family well-being (SWB; 7 items), emotional well-being (EWB; 6 items), and functional well-being (FWB; 7 items). In addition, the FACT-M includes a 16-item disease-specific Melanoma Subscale (MS). Each FACT-M item is rated on a 5-point scale ranging from 0 (not at all) to 4 (very much). Scores for the PWB, FWB, SWB, and EWB subscales can be combined to produce a FACT-G total score, which provides an overall indicant of generic quality of life, while the FACT-G and MS scores can be combined to produce a total score for the FACT-M, which provides a composite measure of general and targeted quality of life. Overall scale ranges from 0 to 172, higher values indicate better functioning as well as lower symptom burden. |
| Peak Serum Concentration (Cmax1) After the First Dose of Nivolumab and Relatlimab | Post-dose Day 1 | Blood samples were collected to assess serum concentration. |
| Maximum Observed Concentration at Steady State (Cmaxss) Nivolumab and Relatlimab | Post-dose Day 1 | Blood samples were collected to assess serum concentration. |
| Average Observed Concentration at Steady State (Cavgss) of Nivolumab and Relatlimab | Post-dose Day 1 | Blood samples were collected to assess serum concentration. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Finland, France, Germany, Israel, Italy, Norway, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 13.59 |
| Age, Customized 18-64 years | 277 Participants |
| Age, Customized 65-84 years | 288 Participants |
| Age, Customized 85 years and over | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 209 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African-American | 3 Participants |
| Race/Ethnicity, Customized Multiple | 6 Participants |
| Race/Ethnicity, Customized Unknown | 59 Participants |
| Race/Ethnicity, Customized White | 503 Participants |
| Sex: Female, Male Female | 229 Participants |
| Sex: Female, Male Male | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 80 / 286 | 63 / 292 |
| other Total, other adverse events | 242 / 283 | 261 / 291 |
| serious Total, serious adverse events | 143 / 283 | 140 / 291 |
Outcome results
None listed