Clinical trial NCT06504394: 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)
Official title: A Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Pembrolizumab 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Classical Hodgkin Lymphoma Recurrent
Classical Hodgkin Lymphoma Refractory
Primary Mediastinal Large B-cell Lymphoma Recurrent
Primary Mediastinal Large B-cell Lymphoma Refractory
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-07-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator
timeFrame: Up to approximately 48 months
measure: Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
timeFrame: At designated time points (up to ~6 weeks)
measure: Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
timeFrame: At designated time points (up to ~6 weeks)
measure: Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks)
timeFrame: At designated time points (up to ~6 weeks)
Secondary outcomes:
measure: Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator
timeFrame: Up to approximately 48 months
measure: Number of Participants with Antidrug Antibodies (ADA) Level of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
timeFrame: At designated timepoints (Up to approximately 27 months)
measure: Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State
timeFrame: At designated time points (up to ~6 weeks)
measure: Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady State
timeFrame: At designated time points (up to ~6 weeks)
measure: 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
timeFrame: At designated time points (up to ~6 weeks)
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to approximately 30 months
measure: Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Westbury
country: United States
facility: Clinical Research Alliance ( Site 0101)
state: New York
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 0901)
state: New South Wales
city: Concepcion.
country: Chile
facility: Biocenter ( Site 0203)
state: Biobio
city: La Serena.
country: Chile
facility: IC La Serena Research ( Site 0204)
state: Coquimbo
city: Santiago
country: Chile
facility: FALP ( Site 0207)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica Inmunocel ( Site 0201)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 0202)
state: Region M. De Santiago
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 1302)
state: Nordrhein-Westfalen
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Oncology ( Site 1101)
city: Ciudad de México
country: Mexico
facility: Health Pharma Professional Research S.A. de C.V: ( Site 0403)
state: Distrito Federal
city: Oaxaca
country: Mexico
facility: Centro de Investigacion Clinica de Oaxaca ( Site 0405)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 1001)
city: Krakow
country: Poland
facility: Pratia MCM Krakow ( Site 0503)
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 0501)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0502)
state: Pomorskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0504)
state: Slaskie
city: L'Hospitalet Del Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet-Haematology Department ( Site 0703)
state: Barcelona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca ( Site 0702)
state: Castilla Y Leon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre-Hemathology and hemotherapy ( Site 0701)
city: Ankara
country: Turkey
facility: Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 0801)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri ( Site 0802)
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi ( Site 0803)
city: Bodelwyddan
country: United Kingdom
facility: Glan Clwyd Hospital ( Site 0602)
state: Denbighshire
city: London
country: United Kingdom
facility: University College London Hospital ( Site 0605)
state: London, City Of
city: Oxford
country: United Kingdom
facility: Churchill Hospital ( Site 0604)
state: Oxfordshire
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust ( Site 0603)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: