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.
John Timmerman, David Lavie, Nathalie A. Johnson, Abraham Avigdor, Peter Borchmann, Charalambos Andreadis, Ali Bazargan, Gareth P. Gregory, Colm Keane, Inna Tzoran, Vladan Vucinic, Pier Luigi Zinzani, Rachel Marceau West, Pallavi Pillai, Rushdia Yusuf, Alex F. Herrera