Estimating efficacy of favezelimab plus pembrolizumab relative to pembrolizumab in anti-PD-1-refractory Hodgkin lymphoma.

Favezelimab plus pembrolizumab had promising efficacy in anti-programmed cell death protein 1 (PD-1)-refractory classical Hodgkin lymphoma in MK-4280-003; however, the contribution of favezelimab was unclear. Here, we assessed the relative contribution of favezelimab by comparison with data from participants treated with only pembrolizumab beyond progression in KEYNOTE-087. Participants in MK-4280-003 had received ≥2 doses of anti-PD-1 therapy and progressed <12 weeks of last dose. Participants eligible from KEYNOTE-087 had received >2 doses of pembrolizumab beyond progression, and progressed <12 weeks of last dose. Participants received pembrolizumab 200 mg plus favezelimab 200 mg or 800 mg, or pembrolizumab 200 mg IV every 3 weeks. Change in target lesion size and response per International Working Group 2007 criteria were assessed. Baseline tumor size was reset at first progression for KEYNOTE-087. A bootstrapping method compared change in target lesion size between groups. Twenty-seven participants from MK-4280-003 and 81 from KEYNOTE-087 were included. Objective response rates were 37% (95% confidence interval [CI], 15-51) for favezelimab plus pembrolizumab, and 2% (95% CI, 0-6) for pembrolizumab alone. A clinically meaningful reduction (≥50%) in target lesion size was observed in 13 (48%) vs 4 participants (5%), respectively. The mean change from baseline in target lesion size was -49% and -0.4%. In the bootstrapping analysis, 99.4% of samples showed greater decrease in tumor burden with favezelimab plus pembrolizumab. Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone in anti-PD-1-refractory classical Hodgkin lymphoma, suggesting favezelimab contributed substantially to efficacy in MK-4280-003. The trials were registered at www.clinicaltrials.gov as #NCT03598608 and #NCT02453594.