Favezelimab (anti–LAG-3) + pembrolizumab (PD-1) reports 83% ORR in PD-1–naive R/R cHL; development discontinued

Favezelimab (MK-4280) is an anti–LAG-3 monoclonal antibody designed to deepen checkpoint blockade when combined with pembrolizumab (anti–PD-1); this Phase 1/2 MK-4280-003 cohort enrolled anti–PD-1–naive relapsed/refractory classical Hodgkin lymphoma patients (n=30) and treated them at the RP2D (favezelimab 800mg + pembrolizumab 200mg IV Q3W; NCT03598608). ORR was 83% with a 37% CR rate; median DOR was 17.0 months and median PFS was 19.4 months (24-month PFS 46%), with median OS not reached and 24-month OS 93%; by comparison, pembrolizumab monotherapy in R/R cHL has reported ORR ~69–71% and CR ~22–28% with median PFS ~13.7 months (KEYNOTE-087), so the efficacy here looks numerically higher but cross-trial. Safety was broadly in-family for checkpoint combos: in cohort 1, 90% had treatment-related AEs, 23% had grade 3–4 TRAEs, and 17% discontinued; a DLT occurred in 1/21 patients in the safety lead-in (grade 4 autoimmune hepatitis).

Merck announced discontinuation of the favezelimab clinical development program on December 16, 2024, including stopping enrollment in the Phase 3 KEYFORM-008 trial while allowing already-enrolled patients to continue treatment. These newly published findings therefore inform the evidence for combined LAG-3/PD-1 blockade rather than establish an actively advancing treatment option.