This study will assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of escalating doses of quavonlimab when used in combination with pembrolizumab in participants with advanced solid tumors.
Name: Quavonlimab
Name: Pembrolizumab
Name: Pembrolizumab/Quavonlimab
Name: cisplatin
Name: carboplatin
Name: pemetrexed
Name: nab-paclitaxel
Name: paclitaxel
Description: DLTs will be assessed during the first 6 weeks (2 cycles) of treatment for the Dose Escalation and the first 3 weeks (1 cycle) of treatment for the Dose Confirmation. DLT is defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.
Measure: Number of participants with a Dose Limiting Toxicity (DLT) Time: Up to 6 weeksDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure: Number of participants with ≥1 adverse event (AE) Time: Up to approximately 2.5 yearsDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure: Number of participants discontinuing study treatment due to an AE Time: Up to approximately 2 yearsDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure: Coformulation Phase: Number of participants with ≥1 AE Time: Up to approximately 2.5 yearsDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure: Coformulation Phase: Number of participants discontinuing study treatment due to an AE Time: Up to approximately 2 yearsDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure: Efficacy Expansion: Number of participants with ≥1 AE Time: Up to approximately 2.5 yearsDescription: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment
Measure: Efficacy Expansion: Number of participants discontinuing study treatment due to an AE Time: Up to approximately 2 yearsDescription: ORR is defined as the percentage of participants in the analysis population whose best overall response (BOR) is confirmed complete response (CR) or partial response (PR) as assessed by BICR and based on imaging per modified RECIST 1.1. Tumor responses evaluated using modified RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to modified RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to modified RECIST 1.1 is at least a 30% decrease in the sum of diameters (SOD) of target lesions as assessed by the investigator, taking as reference the baseline SOD.
Measure: Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Time: Up to approximately 4 yearsDescription: DLTs will be assessed during the first 6 weeks of treatment for the Coformulation Phase for Arms I and L. A DLT is defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 of the Coformulation Phase due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.
Measure: Coformulation Phase: Number of participants with ≥1 DLT Time: Up to 6 weeksDescription: ORR is defined as the percentage of participants in the analysis population whose best overall response (BOR) is confirmed complete response (CR) or partial response (PR) as assessed by BICR and based on imaging per modified RECIST 1.1. Tumor responses evaluated using modified RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to modified RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to modified RECIST 1.1 is at least a 30% decrease in the sum of diameters (SOD) of target lesions as assessed by the investigator, taking as reference the baseline SOD.
Measure: Coformulation Phase: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Time: Up to approximately 4 yearsDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Dose Escalation: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 5, 9. Cycle length = 21 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Dose Escalation: Minimum concentration (Cmin) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 5, 9. Pre-dose at Cycles 6, 7, and every 4 cycles after Cycle 9 up to 2 years. Cycle length = 21 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Dose Escalation: Maximum concentration (Cmax) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 5, 9. Cycle length = 21 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Dose Escalation: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 2, 3, 5, 9. Cycle length = 21 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Dose Escalation: Minimum concentration (Cmin) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 2, 3, 5, 9. Pre-dose at Cycles 6, 7, and every 4 cycles after Cycle 9 up to 2 years. Cycle length = 21 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Dose Escalation: Maximum concentration (Cmax) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 2, 3, 5, 9. Cycle length = 21 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Dose Escalation: Quavonlimab anti-drug antibody levels Time: Pre-dose at Cycles 1 through 9 and every 4 cycles up to 2 years. Cycle length = 21 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Dose Escalation: Pembrolizumab anti-drug antibody levels Time: Pre-dose at Cycles 1 through 9 and every 4 cycles up to 2 years. Cycle length = 21 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Dose Confirmation: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Dose Confirmation: Minimum concentration (Cmin) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Pre-dose at Cycles 5, 6, and every 4 cycles after Cycle 8 up to 2 years. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Dose Confirmation: Maximum concentration (Cmax) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Dose Confirmation: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Dose Confirmation: Minimum concentration (Cmin) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Pre-dose at Cycles 5, 6, and every 4 cycles after Cycle 8 up to 2 years. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Dose Confirmation: Maximum concentration (Cmax) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 15) for Cycles 1, 2, 3, 4, and 8. Cycle length = 21 days. No post-dose samples for Cycles 2, 4, and 8 for Arms B, C, and D.Description: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Dose Confirmation: Quavonlimab anti-drug antibody levels Time: Pre-dose at Cycles 1 through 9 and every 4 cycles up to 2 years. Cycle length = 21 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Dose Confirmation: Pembrolizumab anti-drug antibody levels Time: Pre-dose at Cycles 1 through 9 and every 4 cycles up to 2 years. Cycle length = 21 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Efficacy Expansion: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Efficacy Expansion: Minimum concentration (Cmin) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Efficacy Expansion: Maximum concentration (Cmax) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Efficacy Expansion: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Efficacy Expansion: Minimum concentration (Cmin) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Efficacy Expansion: Maximum concentration (Cmax) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Efficacy Expansion: Quavonlimab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Efficacy Expansion: Pembrolizumab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Coformulation Phase: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Coformulation Phase: Minimum concentration (Cmin) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Coformulation Phase: Maximum concentration (Cmax) of quavonlimab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Coformulation Phase: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Coformulation Phase: Minimum concentration (Cmin) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Coformulation Phase: Maximum concentration (Cmax) of pembrolizumab Time: Pre-dose Day 1 and post-dose Day 21 for Cycles 1 through 4. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Coformulation Phase: Quavonlimab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Coformulation Phase: Pembrolizumab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Japanese Cohort: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Japanese Cohort: Minimum concentration (Cmin) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Pre-dose at every 4 cycles after Cycle 4 up to 2 years. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Japanese Cohort: Maximum concentration (Cmax) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Japanese Cohort: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Japanese Cohort: Minimum concentration (Cmin) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Pre-dose at every 4 cycles after Cycle 4 up to 2 years. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Japanese Cohort: Maximum concentration (Cmax) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Japanese Cohort: Quavonlimab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. After Cycle 4 pre-dose for every 2 cycles up to 2 years. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Japanese Cohort: Pembrolizumab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. After Cycle 4 pre-dose for every 2 cycles up to 2 years. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of quavonlimab.
Measure: Chinese Cohort: Area under the plasma concentration time curve (AUC) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of quavonlimab.
Measure: Chinese Cohort: Minimum concentration (Cmin) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Pre-dose at every 4 cycles after Cycle 4 up to 2 years. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of quavonlimab.
Measure: Chinese Cohort: Maximum concentration (Cmax) of quavonlimab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: AUC is the area under the plot of plasma concentration of drug against time after drug administration. Blood samples will be collected at multiple time points to assess the AUC of pembrolizumab.
Measure: Chinese Cohort: Area under the plasma concentration time curve (AUC) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Cmin is the minimum or "trough" concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. Blood samples will be collected at multiple time points to assess the Cmin of pembrolizumab.
Measure: Chinese Cohort: Minimum concentration (Cmin) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Pre-dose at every 4 cycles after Cycle 4 up to 2 years. Cycle length = 42 daysDescription: Cmax is the maximum or "peak" concentration of a drug observed after its administration. Blood samples will be collected at multiple time points to assess the Cmax of pembrolizumab.
Measure: Chinese Cohort: Maximum concentration (Cmax) of pembrolizumab Time: Pre- and post-dose at multiple time points (up to Day 21) for Cycles 1 through 4. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of quavonlimab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Chinese Cohort: Quavonlimab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. After Cycle 4 pre-dose for every 2 cycles up to 2 years. Cycle length = 42 daysDescription: Blood samples will be collected at designated time points for the determination of the presence or absence of pembrolizumab anti-drug antibodies. The percentage of participants who develop anti- antibodies will be presented.
Measure: Chinese Cohort: Pembrolizumab anti-drug antibody levels Time: Pre-dose Cycles 1 through 4 on Day 1. After Cycle 4 pre-dose for every 2 cycles up to 2 years. Cycle length = 42 daysDescription: ORR is defined as the percentage of participants in the analysis population whose BOR is confirmed CR or PR as assessed by investigator and based on imaging per modified RECIST 1.1. Tumor responses evaluated using modified RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to modified RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to modified RECIST 1.1 is at least a 30% decrease in the SOD of target lesions as assessed by the investigator, taking as reference the baseline SOD.
Measure: Dose Escalation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1 Time: Up to approximately 4 yearsDescription: ORR is defined as the percentage of participants in the analysis population whose BOR is confirmed CR or PR as assessed by investigator and based on imaging per modified RECIST 1.1. Tumor responses evaluated using modified RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to modified RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to modified RECIST 1.1 is at least a 30% decrease in the SOD of target lesions as assessed by the investigator, taking as reference the baseline SOD.
Measure: Dose Confirmation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1 Time: Up to approximately 4 yearsDescription: ORR is defined as the percentage of participants in the analysis population whose BOR is confirmed CR or PR as assessed by investigator and based on imaging per modified RECIST 1.1. Tumor responses evaluated using modified RECIST 1.1 follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ and require confirmation per RECIST 1.1. According to modified RECIST 1.1, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR according to modified RECIST 1.1 is at least a 30% decrease in the SOD of target lesions as assessed by the investigator, taking as reference the baseline SOD.
Measure: Coformulation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1 Time: Up to approximately 4 yearsDescription: DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first (for responders only).
Measure: Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on modified RECIST Version 1.1 Time: Up to approximately 4 yearsDescription: DOR was defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first (for responders only).
Measure: Coformulation: Duration of Response (DOR) as assessed by BICR based on modified RECIST Version 1.1 Time: Up to approximately 4 yearsAllocation: Non-Randomized
Parallel Assignment
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Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions - Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed) - Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible - Have submitted pre-trial imaging and provided a baseline tumor sample - Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment - BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. --- V600E ---