A Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Coformulated With Hyaluronidase (MK-3475A) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)(MK-3475A-F65)
NCT Number: NCT06504394
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Classical Hodgkin Lymphoma Recurrent|Classical Hodgkin Lymphoma Refractory|Primary Mediastinal Large B-cell Lymphoma Recurrent|Primary Mediastinal Large B-cell Lymphoma Refractory
Interventions: BIOLOGICAL: Pembrolizumab Coformulated With Hyaluronidase
Sponsor: Merck Sharp & Dohme LLC
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-29
Completion Date: 2028-11-08
Locations: Clinical Research Alliance ( Site 0101), Westbury, New York, 11590, United States

Summary:
The primary purpose of the study is to assess the pharmacokinetics (PK) profile of pembrolizumab (MK-3475) following subcutaneous (SC) injection of pembrolizumab coformulated with hyaluronidase (MK-3475A), and to evaluate the objective response rate (ORR) of MK-3475A SC in adult participants with Relapsed or Refractory Classical Hodgkin Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL). There is no formal hypothesis to be tested for this study.

Primary Outcome Measures: Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator, ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. Response was assessed based on the International Working Group Criteria: Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). The percentage of participants who experience CR or PR as assessed by investigator will be presented., Up to approximately 50 months|Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase, Blood samples will be collected at designated timepoints for the determination of Cmax. Cmax is defined as the peak concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase., At designated time points (up to ~6 weeks)|Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase, Blood samples will be collected at designated timepoints for the determination of Ctrough. Ctrough is defined as the lowest concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase., At designated time points (up to ~6 weeks)|Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks), Blood samples will be collected at designated timepoints for the determination of AUC0-6weeks. AUC0-6 weeks is defined as area under concentration time curve over a 6-week dosing interval of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase., At designated time points (up to ~6 weeks)
Secondary Outcome Measures: Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator, For participants who demonstrate a confirmed complete response (CR) or partial response (PR), DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using computed tomography (CT) and positron emission tomography (PET)-CT and response was evaluated based on the Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters (SPD) for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). DOR as assessed by the investigator will be presented., Up to approximately 50 months|Number of Participants with Antidrug Antibodies (ADA) Level of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase, Blood samples will be collected at designated time points for the determination of the presence or absence of ADA of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase. The number of participants who develop ADA will be reported., At designated timepoints (Up to approximately 27 months)|Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State, Blood samples will be collected at designated timepoints for the determination of Cmax. Cmax is defined as the peak concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase at steady state., At designated time points (up to ~6 weeks)|Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State, Blood samples will be collected at designated timepoints for the determination of Ctrough. Ctrough is defined as the lowest concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase at steady state., At designated time points (up to ~6 weeks)|Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks) at Steady State, Blood samples will be collected at designated timepoints for the determination of AUC0-6weeks. AUC0-6 weeks is defined as area under concentration time curve over a 6-week dosing interval of pembrolizumab coformulated with hyaluronidase at steady state., At designated time points (up to ~6 weeks)|Number of Participants Experiencing an Adverse Event (AE), An AE is defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of participants who experience an AE will be reported., Up to approximately 30 months|Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE), An AE is defined as any untoward medical occurrence in a participant administered a study treatment which did not necessarily have to have a causal relationship with this treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported., Up to approximately 2 years