Phase 1/2 study of favezelimab plus pembrolizumab in anti-PD-1-naive relapsed or refractory classical Hodgkin lymphoma.

The phase 1/2 MK-4280-003 study evaluated favezelimab plus pembrolizumab for relapsed or refractory (R/R) hematologic malignancies. We report results in anti-PD-1-naive R/R classical Hodgkin lymphoma (cHL; cohort 1). The study comprised a safety lead-in (across 4 cohorts) to establish the recommended phase 2 dose (RP2D) of favezelimab plus pembrolizumab and an efficacy expansion phase (pembrolizumab 200 mg plus favezelimab at RP2D intravenously [IV] every 3 weeks [Q3W]). Adults with anti-PD-1-naive R/R cHL were enrolled in cohort 1. Primary end point was safety (dose-limiting toxicity [DLT], adverse events [AEs], and AEs leading to discontinuation) to establish RP2D. Objective response rate (ORR) was secondary. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. RP2D was favezelimab 800 mg plus pembrolizumab 200 mg IV Q3W. DLT occurred in 1 of 21 participants in the safety lead-in (grade 4 autoimmune hepatitis). Cohort 1 enrolled 30 participants. Treatment-related AEs occurred in 27 participants (90%; grade 3 or 4 in 7 participants [23%]; no grade 5), and 5 participants (17%) discontinued treatment. ORR was 83% (95% CI, 65-94); complete response rate was 37% (95% CI, 20-56). Median DOR was 17.0 months (range, 2.6-33.3+); an estimated 44% of responders continued to have responses after ≥24 months. Median PFS was 19.4 months (95% CI, 9.5-28.5); 24-month PFS rate was 46%. Median OS was not reached (NR; 95% CI, 46.9-NR); 24-month OS rate was 93%. Favezelimab plus pembrolizumab showed antitumor activity and manageable safety in participants with anti-PD-1-naive R/R cHL. This trial was registered at www.ClinicalTrials.gov as NCT03598608.