Background: The immune checkpoint receptor LAG-3 may contribute to anti–PD-1 resistance in patients (pts) with relapsed or refractory (R/R) cHL. In a multicohort phase 1/2 study (NCT03598608), pembro + the anti–LAG-3 antibody favezelimab demonstrated manageable safety and promising antitumor activity in pts with heavily pretreated cHL whose disease progressed on or after anti–PD-1 therapy (cohort 2). Updated results with additional follow-up from cohort 2 are presented.
Methods: Eligible pts (aged ≥18 y) had R/R cHL and had no response to or whose disease progressed after autologous stem cell transplantation (ASCT), were ineligible for ASCT, or had no response to salvage chemotherapy. Pts in cohort 2 had disease progression after ≥2 doses of anti–PD-1–based therapy and within 12 wks of last dose. Study comprised a safety lead-in followed by efficacy expansion. In safety lead-in, all pts received pembro 200 mg IV Q3W + favezelimab 200-mg starting dose with escalation to 800 mg IV Q3W per a modified toxicity probability interval design. In efficacy expansion, pts received pembro 200 mg Q3W + favezelimab at the RP2D of 800 mg Q3W for ≤35 cycles. Primary end point: safety. ORR per IWG 2007 criteria by investigator review was a secondary end point. Exploratory end points included DOR and PFS per IWG 2007 criteria by investigator review and OS. Data cutoff was February 22, 2024.
Results: Cohort 2 included 34 pts. Median time from first dose to data cutoff was 47.0 mo (range, 26.7-61.1). Treatment-related adverse events (TRAEs) occurred in 28 pts (82%; grade 3 or 4 in 6 pts [18%]). TRAEs led to treatment discontinuation in 6 pts (18%). No pts died due to TRAEs. AEs of clinical interest occurred in 17 pts (50%); 2 (6%) had grade 3 events (encephalitis, hepatitis) and 1 (3%) had grade 4 type 1 diabetes mellitus. ORR was 29% (95% CI, 15-48%; 3 CR; 7 PR). Median DOR was 21.9 mo (range, 0.0+ to 26.1+). Median PFS was 9.7 mo (95% CI, 5.1-14.7) and median OS was not reached (95% CI, 27.9-not reached).
Conclusion: With additional follow-up, pembro plus favezelimab continued to demonstrate manageable safety and sustained antitumor activity in pts with heavily pretreated anti–PD-1–refractory R/R cHL. A coformulation of favezelimab and pembro is being evaluated (KEYFORM-008; NCT05508867).
©2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 ASCO Annual Meeting. All rights reserved.