ISHL12 Abstract 174

Safety and Dose-Expansion Study of Combination Favezelimab (anti–LAG-3) Plus Pembrolizumab in Anti–PD-1–Naive Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Background: PD-1 inhibitors play a key role in the treatment of relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), yet novel strategies to enhance responses remain of clinical interest. The multicohort phase 1/2 MK-4280-003 study (NCT03598608) evaluated the safety and efficacy of a LAG-3 inhibitor, favezelimab (MK-4280), + pembrolizumab (pembro) in pts with R/R hematologic malignancies. Cohort 1 focused on anti–PD-1–naive pts with R/R cHL.

Methods: Part 1 was the safety lead-in phase to determine the recommended phase 2 dose (RP2D) followed by a dose-expansion phase (part 2). Eligible pts in cohort 1 had R/R cHL after autologous stem cell transplantation (ASCT), were ineligible for ASCT, and had no prior anti–PD-1 therapy. Part 1 included pts from all cohorts who received escalating doses (per mTPI design) of pembro IV 200 mg Q3W and favezelimab IV 200 mg or 800 mg Q3W. In part 2, pts received pembro + favezelimab at the established RP2D for ≤35 cycles. The primary end point was safety. ORR was a secondary end point. DOR, PFS, and OS were exploratory end points. Database cutoff was March 21, 2022.

Results: Part 1 identified 1 dose-limiting toxicity (DLT; autoimmune hepatitis [grade 4]) among the first 6 pts from all cohorts at the favezelimab 200 mg dose. No DLTs were found after an additional 15 pts at the 800 mg dose; RP2D was defined as 800 mg Q3W + pembro 200 mg Q3W. Of the 30 pts in cohort 1, median age was 40.5 y, 53% had ECOG PS 0, and 80% had ≤3 prior lines of therapy. At database cutoff, 12 of 30 pts had discontinued (4 AEs; 8 PD; 13% due to treatment-related AEs [TRAEs]). No deaths were treatment related. 26 pts (87%) had TRAEs; the most common (≥20%) were hypothyroidism (27%), infusion-related reactions (23%), and fatigue (20%); 7 pts (23%) had grade 3 or 4 TRAEs. After median follow-up of 14.1 mo, ORR was 73% (95% CI, 54-88; CR, 8 [27%]; PR, 14 [47%]). 28 of 29 pts (97%) who received a postdose scan had a baseline reduction in target lesions. Median DOR was not reached (NR; range, 2.6-25.9+ mo); 7 pts (55%) had response ≥12 mo. Median PFS was 19.4 mo (range, 8.5 mo-NR) and median OS was NR (range, NR-NR).

Conclusion: Favezelimab 800 mg + pembro 200 mg Q3W demonstrated acceptable safety and effective antitumor activity in anti–PD-1–naive pts with R/R cHL. Comparative studies on its activity to that of single-agent pembro would be of clinical benefit.