Favezelimab plus pembrolizumab for anti-PD-1-refractory classic Hodgkin lymphoma: an open-label phase 1/2 study

The MK-4280-003 study evaluated favezelimab plus pembrolizumab in hematologic malignancies. We report results for anti-programmed cell death protein 1 (PD-1)-refractory classic Hodgkin lymphoma (cHL; cohort 2). Participants in the safety lead-in had relapsed or refractory (R/R) cHL, diffuse large B-cell lymphoma, or indolent B-cell lymphoma. Participants in cohort 2 had R/R cHL, had undergone or were ineligible for autologous stem cell transplantation, and had disease progression after ≥2 doses of anti-PD-1 therapy and within 12 weeks of last dose. Primary end points were safety and the recommended phase 2 dose (RP2D) of favezelimab plus pembrolizumab. Objective response rate (ORR) was secondary. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. In the safety lead-in, 1 of 21 participants experienced a dose-limiting toxicity (grade 4 autoimmune hepatitis). The RP2D was favezelimab 800 mg plus pembrolizumab 200 mg IV every 3 weeks. Cohort 2 included 34 participants. Treatment-related adverse events (AEs) occurred in 28 participants (82%; grade 3 or 4 in 6 participants [18%]; no grade 5 AEs). Immune-mediated AEs and infusion reactions occurred in 17 participants (50%; grade 3 or 4 in 3 participants [9%]; no grade 5 AEs). ORR was 29% (95% confidence interval [CI], 15-48). Median DOR was 21.9 months (range, 0.0+ to 26.1+). Median PFS was 9.7 months (95% CI, 5.1-14.7); 24-month PFS was 21%. Median OS was not reached (NR; 95% CI, 27.9 to NR); 24-month OS was 76%. Favezelimab plus pembrolizumab showed manageable safety and antitumor activity in heavily pretreated anti-PD-1-refractory cHL. This trial was registered at www.clinicaltrials.gov as NCT03598608.