MK-3475A in Relapsed or Refractory Classic Hodgkin Lymphoma or Primary Mediastinal Large B-cell Lymphoma: The Single-arm, Open-label Phase 2 MK-3475A-F65 Study

Introduction/Background/Significance: The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab is a standard-of-care treatment option for multiple cancers, including relapsed or refractory (R/R) classic Hodgkin lymphoma (cHL) and R/R primary mediastinal large B-cell lymphoma (PMBCL). Pembrolizumab is currently administered as an intravenous infusion. Subcutaneous administration of pembrolizumab offers advantages to patients, providers, and the healthcare system. MK-3475A is pembrolizumab with berahyaluronidase alfa for subcutaneous administration (subcutaneous pembrolizumab). Berahyaluronidase alfa, a human hyaluronidase variant developed and manufactured by Alteogen Inc., is a permeation enhancer that increases dispersion and allows for subcutaneous administration of pembrolizumab in a single injection for both every 3 weeks (Q3W) and every 6 weeks (Q6W) dosing. The single-arm, open-label, phase 2 MK-3475A-F65 study (NCT06504394) has been designed to evaluate the pharmacokinetics, efficacy, and safety of subcutaneous pembrolizumab in participants with R/R cHL or R/R PMBCL. The methodology of MK-3475A-F65 is described.

Materials and Methods/Case Presentation/Objective: Eligible participants are aged ≥18 years with a confirmed diagnosis of cHL or PMBCL that is fluorodeoxyglucose-avid per World Health Organization criteria, have radiographically measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Participants with cHL must be anti–PD-1 naive and have not responded to or relapsed after ≥1 line of multi-agent therapy (with or without brentuximab vedotin) or autologous stem cell transplantation (auto-SCT). Participants with PMBCL must be anti–PD-1 naive and have not responded to or relapsed after ≥2 prior lines of therapy (including ≥1 rituximab-based regimen), or are ineligible for, have not responded to, or relapsed after auto-SCT. Participants with clinically significant cardiovascular disease, pericardial effusion or clinically significant pleural effusion, or an additional malignancy that is progressing or has required active treatment within the past 2 years are excluded. All participants will receive subcutaneous pembrolizumab 790 mg Q6W for up to 18 cycles (approximately 2 years). Treatment will continue until disease progression, unacceptable toxicity, withdrawal, or other discontinuation criteria are met. The primary end points are the pharmacokinetics of subcutaneous pembrolizumab during cycle 1 and objective response rate per Lugano classification criteria by investigator review. Secondary end points are pharmacokinetics at steady state (cycle 3), antidrug antibody levels, safety and tolerability, and duration of response per Lugano classification criteria by investigator review. Computed tomography scans will be performed every 12 weeks; positron emission tomography scans will be performed at week 12, week 24, and to confirm complete response. Safety will be monitored throughout the study and for ≤30 days after end of treatment (90 days for serious adverse events; or 30 days if new anticancer therapy is initiated). Adverse events will be graded per National Cancer Institute Common Terminology Criteria for Adverse Events, v5.0.

Results/Description/Main Outcome Measures: Approximately 60 participants will be enrolled. Recruitment is ongoing. ©2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting. All rights reserved.