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)
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 or on the day of the 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 except certain protocol-specified therapies
* 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
Primary outcome measure(s)
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.
Trial sites (29)
Facility
City
Region
Status
University of Iowa-Holden Comprehensive Cancer Center ( Site 0115)
Iowa City
Iowa
University of Iowa - Waukee ( Site 0111)
Waukee
Iowa
Comprehensive Cancer Centers of Nevada ( Site 0114)
Las Vegas
Nevada
Clinical Research Alliance ( Site 0101)
Westbury
New York
Westmead Hospital ( Site 0901)
Westmead
New South Wales
Biocenter ( Site 0203)
Concepción
Biobio
IC La Serena Research ( Site 0204)
La Serena
Coquimbo Region
FALP ( Site 0207)
Santiago
Region M. de Santiago
Clínica Inmunocel ( Site 0201)
Santiago
Region M. de Santiago
Bradfordhill-Clinical Area ( Site 0202)
Santiago
Region M. de Santiago
Universitaetsklinikum Essen ( Site 1302)
Essen
North Rhine-Westphalia
Health Pharma Professional Research S.A. de C.V: ( Site 0403)
Mexico City
Mexico City
Centro de Investigacion Clinica de Oaxaca ( Site 0405)
Oaxaca City
Mexico
Auckland City Hospital ( Site 1001)
Auckland
New Zealand
Pratia MCM Krakow ( Site 0503)
Krakow
Lesser Poland Voivodeship
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 0501)
Warsaw
Masovian Voivodeship
Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0502)
Gdansk
Pomeranian Voivodeship
Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0504)
Gliwice
Silesian Voivodeship
Seoul National University Hospital-Oncology ( Site 1101)
Seoul
South Korea
Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 0703)
L'Hospitalet Del Llobregat
Barcelona
Hospital Universitario de Salamanca ( Site 0702)
Salamanca
Castille and León
Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 0701)
Madrid
Spain
Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 0801)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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