A Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Coformulated With Berahyaluronidase Alfa (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)

Phase 2

Recruiting

• Conditions: Classical Hodgkin Lymphoma Recurrent; Primary Mediastinal Large B-cell Lymphoma Recurrent; Classical Hodgkin Lymphoma Refractory; Primary Mediastinal Large B-cell Lymphoma Refractory
• Interventions: Biological: Pembrolizumab (+) Berahyaluronidase alfa

• Registration Number: NCT06504394
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The primary purpose of the study is to assess the pharmacokinetics (PK) profile of pembrolizumab following subcutaneous (SC) injection of pembrolizumab coformulated with hyaluronidase, and to evaluate the objective response rate (ORR) of pembrolizumab (+) berahyaluronidase alfa 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-11
• Study First Posted: 2024-07-16
• Study Start: 2024-10-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-16
• Primary Completion: 2028-11-08
• Study Completion: 2028-11-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

The main inclusion criteria include but are not limited to the following:

• Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) or primary mediastinal B-cell lymphoma (PMBCL)
• Radiographically measurable cHL or PMBCL disease assessed by investigator as per Lugano classification
• Have a life expectancy of >3 months
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before enrollment
• Participants with history of hepatitis C virus (HCV) infection are eligible if they have completed curative antiviral therapy at least 4 weeks before enrollment and HCV viral load is undetectable at screening
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before first dose of study intervention

Exclusion Criteria

The main exclusion criteria include but are not limited to the following:

• Has clinically significant (i.e., active) cardiovascular disease
• Has pericardial effusion or clinically significant pleural effusion
• Has known additional malignancy that is progressing or has required active treatment within the past 2 years
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
• Received prior monoclonal antibody within 4 weeks prior to first dose of study intervention or has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier
• Received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Received a live or live-attenuated vaccine within 30 days before first dose of study intervention
• Is receiving systemic antineoplastic chemotherapy, immunotherapy, or biological therapy not specified in this protocol
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Active infection requiring systemic therapy
• Concurrent active hepatitis B and hepatitis C virus infection
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplant (SCT) within the last 5 years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab Coformulated With Hyaluronidase	Pembrolizumab (+) Berahyaluronidase alfa	Participants with rrCHL and rrPMBCL receive pembrolizumab coformulated with hyaluronidase subcutaneous (SC) injection on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (approximately 2 years) until documented disease progression per investigator assessment.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator	Up to approximately 48 months	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.
Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase	At designated time points (up to ~6 weeks)	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.
Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase	At designated time points (up to ~6 weeks)	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.
Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks)	At designated time points (up to ~6 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator	Up to approximately 48 months	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.
Number of Participants with Antidrug Antibodies (ADA) Level of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase	At designated timepoints (Up to approximately 27 months)	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.
Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State	At designated time points (up to ~6 weeks)	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.
Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State	At designated time points (up to ~6 weeks)	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.
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	At designated time points (up to ~6 weeks)	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.
Number of Participants Experiencing an Adverse Event (AE)	Up to approximately 30 months	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.
Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)	Up to approximately 2 years	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.

Trial Locations

Locations (26)

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 0501); 🇵🇱 Warszawa, Mazowieckie, Poland

Clinical Research Alliance ( Site 0101); 🇺🇸 Westbury, New York, United States

Westmead Hospital ( Site 0901); 🇦🇺 Westmead, New South Wales, Australia

Biocenter ( Site 0203); 🇨🇱 Concepcion., Biobio, Chile

IC La Serena Research ( Site 0204); 🇨🇱 La Serena., Coquimbo, Chile

FALP ( Site 0207); 🇨🇱 Santiago, Region M. De Santiago, Chile

Clínica Inmunocel ( Site 0201); 🇨🇱 Santiago, Region M. De Santiago, Chile

Bradfordhill-Clinical Area ( Site 0202); 🇨🇱 Santiago, Region M. De Santiago, Chile

Universitaetsklinikum Essen ( Site 1302); 🇩🇪 Essen, Nordrhein-Westfalen, Germany

Seoul National University Hospital-Oncology ( Site 1101); 🇰🇷 Seoul, Korea, Republic of

Health Pharma Professional Research S.A. de C.V: ( Site 0403); 🇲🇽 Ciudad de México, Distrito Federal, Mexico

Centro de Investigacion Clinica de Oaxaca ( Site 0405); 🇲🇽 Oaxaca, Mexico

Auckland City Hospital ( Site 1001); 🇳🇿 Auckland, New Zealand

Pratia MCM Krakow ( Site 0503); 🇵🇱 Krakow, Malopolskie, Poland

Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0502); 🇵🇱 Gdansk, Pomorskie, Poland

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0504); 🇵🇱 Gliwice, Slaskie, Poland

Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 0703); 🇪🇸 L'Hospitalet Del Llobregat, Barcelona, Spain

Hospital Universitario de Salamanca ( Site 0702); 🇪🇸 Salamanca, Castilla Y Leon, Spain

Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 0701); 🇪🇸 Madrid, Spain

Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 0801); 🇹🇷 Ankara, Turkey

Hacettepe Universite Hastaneleri ( Site 0802); 🇹🇷 Ankara, Turkey

Ondokuz Mayıs Universitesi ( Site 0803); 🇹🇷 Samsun, Turkey

Glan Clwyd Hospital ( Site 0602); 🇬🇧 Bodelwyddan, Denbighshire, United Kingdom

University College London Hospital ( Site 0605); 🇬🇧 London, London, City Of, United Kingdom

Churchill Hospital ( Site 0604); 🇬🇧 Oxford, Oxfordshire, United Kingdom

The Christie NHS Foundation Trust ( Site 0603); 🇬🇧 Manchester, United Kingdom