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)

NCT06504394 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: 3475A-F65MK-3475A-0652024-510969-42-00U1111-1302-8349
• Study Type: interventional
• Target: 66
• Locations: 11 countries
• Sites: 29

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.

Conditions

Classical Hodgkin Lymphoma Refractory; Primary Mediastinal Large B-cell Lymphoma Recurrent; Primary Mediastinal Large B-cell Lymphoma Refractory; Classical Hodgkin Lymphoma Recurrent

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death-2 (PD2, PD-2); Programmed Death-Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (4)

• 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 48 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 Outcomes (7)

• Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator

  Up to approximately 48 months

• 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)

• Maximum Concentration (Cmax) 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

  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

  At designated time points (up to ~6 weeks)

Study Arms (1)

Pembrolizumab Coformulated With Hyaluronidase

EXPERIMENTAL

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.

Biological: Pembrolizumab (+) Berahyaluronidase alfa

Interventions

Pembrolizumab (+) Berahyaluronidase alfa BIOLOGICAL

SC injection

Also known as: MK-3475A

Pembrolizumab Coformulated With Hyaluronidase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or on the day of the first dose of study intervention

You may not qualify if:

• 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 except certain protocol-specified therapies
• Concurrent active hepatitis B and hepatitis C virus infection

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (29)

University of Iowa-Holden Comprehensive Cancer Center ( Site 0115)

Iowa City, Iowa, 52242, United States

Location

University of Iowa - Waukee ( Site 0111)

Waukee, Iowa, 50263, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 0114)

Las Vegas, Nevada, 89169, United States

Location

Clinical Research Alliance ( Site 0101)

Westbury, New York, 11590, United States

Location

Westmead Hospital ( Site 0901)

Westmead, New South Wales, 2145, Australia

Location

IC La Serena Research ( Site 0204)

La Serena, Coquimbo Region, 1720430, Chile

Location

FALP ( Site 0207)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Clínica Inmunocel ( Site 0201)

Santiago, Region M. de Santiago, 7580206, Chile

Location

Bradfordhill-Clinical Area ( Site 0202)

Santiago, Region M. de Santiago, 8420383, Chile

Location

Biocenter ( Site 0203)

Concepción, Región del Biobío, 4070196, Chile

Location

Universitaetsklinikum Essen ( Site 1302)

Essen, North Rhine-Westphalia, 45147, Germany

Location

Health Pharma Professional Research S.A. de C.V: ( Site 0403)

Mexico City, Mexico City, 03100, Mexico

Location

Centro de Investigacion Clinica de Oaxaca ( Site 0405)

Oaxaca City, 68020, Mexico

Location

Auckland City Hospital ( Site 1001)

Auckland, 1023, New Zealand

Location

Pratia MCM Krakow ( Site 0503)

Krakow, Lesser Poland Voivodeship, 30-727, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 0501)

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0502)

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0504)

Gliwice, Silesian Voivodeship, 44-102, Poland

Location

Seoul National University Hospital-Oncology ( Site 1101)

Seoul, 03080, South Korea

Location

Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 0703)

L'Hospitalet Del Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario de Salamanca ( Site 0702)

Salamanca, Castille and León, 37007, Spain

Location

Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 0701)

Madrid, 28041, Spain

Location

Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 0801)

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Universite Hastaneleri ( Site 0802)

Ankara, 06230, Turkey (Türkiye)

Location

Ondokuz Mayıs Universitesi ( Site 0803)

Samsun, 55270, Turkey (Türkiye)

Location

Glan Clwyd Hospital ( Site 0602)

Bodelwyddan, Denbighshire, LL18 5UJ, United Kingdom

Location

University College London Hospital ( Site 0605)

London, London, City of, NW1 2PG, United Kingdom

Location

Churchill Hospital ( Site 0604)

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 0603)

Manchester, m20 4bx, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 16, 2024
• Study Start: October 14, 2024
• Primary Completion (Estimated): November 8, 2028
• Study Completion (Estimated): November 8, 2028
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

ME (2); AU (1); ES (3); NZ (1); CL (5); DE (1); PL (4); KR (1); GB (4); TU (3); US (4)