An open-label phase 1/2 study of favezelimab plus pembrolizumab in patients with relapsed/refractory classical Hodgkin lymphoma with/without previous anti-PD-1 treatment

Introduction: Dual blockade of PD-1 and lymphocyte-activation gene (LAG-3) has shown antitumor activity; however, the activity of the combination for patients (pts) with relapsed or refractory (R/R) classical Hodgkin’s lymphoma (cHL) is unclear. Initial results of a multicohort phase 1/2 study (NCT03598608) showed that the anti–PD-1 inhibitor pembrolizumab (200 mg Q3W) combined with the anti–LAG-3 inhibitor favezelimab (800 mg Q3W) showed promising antitumor activity and acceptable safety in pts with R/R cHL who either were anti–PD-1 naive (cohort 1) or had progression after anti–PD-1 therapy (cohort 2) (Johnson NA et al. J Clin Oncol. 2022;40(16 suppl):7516; Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). Updated data with additional follow-up from both cohorts are presented.

Methods: Pts in cohorts 1 and 2 had R/R cHL after autologous stem cell transplant (ASCT) (or were ineligible for ASCT) or did not respond to salvage chemotherapy and had an ECOG PS of 0 or 1. Pts in cohort 1 had no prior anti–PD-1 therapy; pts in cohort 2 had progression within 12 weeks after ≥2 doses of anti–PD-1 therapy, per Cheson 2007 criteria. Pts received pembrolizumab 200 mg Q3W plus favezelimab at the established RP2D (800 mg Q3W) for ≤35 cycles (∼2 years). Primary end points were safety and RP2D. The secondary end point was ORR. DOR, PFS, and OS were exploratory.

Results: At the data cutoff (Aug 31, 2022), median follow-up (range) was 25.5 (18.0–37.2) months and 29.3 (9.0–43.4) months in cohort 1 and cohort 2, respectively. Anti–PD-1 was the most recent therapy for 17 pts (50%) in cohort 2. In cohort 1, 47% (14 pts) of pts discontinued treatment, and 74% (25 pts) discontinued treatment in cohort 2. ORR was 80% in cohort 1 (95% CI, 61%–92%, 10 CR, 14 PR) and 29% in cohort 2 (95% CI, 15%–47%, 3 CR, 7 PR). Additional efficacy analyses are included in the Table. Treatment-related adverse events (AEs) occurred in 26 pts (87%) and 28 pts (82%) in cohorts 1 and 2, respectively. The most common treatment-related AEs were hypothyroidism (27%) in cohort 1 and hypothyroidism and nausea (18% each) in cohort 2. Grade 3/4 AEs occurred in 7 pts (23%) in cohort 1 and in 6 pts (18%) in cohort 2. No treatment-related deaths occurred.