Favezelimab (LAG-3 mAb) + pembrolizumab (PD-1) posts 29% ORR in PD-1–refractory cHL

Favezelimab is an anti–LAG-3 monoclonal antibody designed to deepen checkpoint blockade when combined with pembrolizumab (anti–PD-1). In the open-label MK-4280-003 Phase 1/2 study (NCT03598608), anti–PD-1–refractory relapsed/refractory classic Hodgkin lymphoma patients post-ASCT or ASCT-ineligible (n=34) received favezelimab 800mg + pembrolizumab 200mg IV Q3W (RP2D); ORR was 29% (95% CI, 15-48), median DOR 21.9 months, median PFS 9.7 months (24-mo PFS 21%), and median OS NR (24-mo OS 76%). TRAEs occurred in 82% with grade 3/4 in 18% and no grade 5 events; immune-mediated AEs/infusion reactions were 50% (grade 3/4 9%), with a safety lead-in DLT of grade 4 autoimmune hepatitis (1/21)—in context, PD-1 monotherapy in earlier-line R/R cHL typically produces ~70% ORR (KEYNOTE-087), so the key question is whether the ~29% ORR here is meaningfully above what you’d expect from PD-1 “rechallenge” in truly PD-1–refractory disease.