Abstract P137

Updated Analysis of a Phase 1/2 Study Evaluating Pembrolizumab (pembro) Plus the Anti–Lymphocyte-Activation Gene 3 (LAG-3) Antibody Favezelimab for Anti–PD-1–Naive Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL)

Background: Dual blockade of PD-1 and the immune checkpoint receptor LAG-3 shows promise as a treatment option for patients (pts) with R/R cHL. In a multicohort phase 1/2 study (NCT03598608), pembro + the anti–LAG-3 antibody favezelimab demonstrated acceptable safety and sustained antitumor activity in pts with R/R cHL who were previously naïve to PD-1 inhibitor therapy (cohort 1). Here, we present updated results with additional follow-up for pts from cohort 1.

Methods: Eligible pts (aged ≥18 y) had R/R cHL and were ineligible for autologous stem cell transplantation (ASCT), whose disease failed to respond to or progressed after ASCT, or who did not respond to salvage chemotherapy. Pts in cohort 1 were naïve to prior PD-1 inhibitor therapy. The study comprised a safety lead-in to determine the recommended phase 2 dose (RP2D) followed by an efficacy expansion phase. 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 method. In efficacy expansion, all pts received pembro 200 mg Q3W + favezelimab at the RP2D of 800 mg Q3W for ≤35 cycles. Primary end point: safety and tolerability. 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 1 included 30 pts. Median time from first dose to data cutoff was 43.2 mo (range, 35.7-54.9). Treatment-related adverse events (TRAEs) occurred in 27 pts (90%; grade 3 or 4 in 7 pts [23%]). TRAEs led to treatment discontinuation in 5 pts (17%). No pts died due to TRAEs. AEs of clinical interest occurred in 20 pts (67%); 3 pts (10%) had grade 3 events (colitis, pneumonitis, severe skin reaction); 1 pt (3%) had grade 4 hepatitis. ORR was 83% (95% CI, 65-94%; 11 CR; 14 PR). Median DOR was 17.0 mo (range, 2.6 to 33.3+). Median PFS was 19.4 mo (95% CI, 9.5-28.5); median OS was not reached (95% CI, 46.9 mo to not reached).

Conclusion: With additional follow-up, pembro + favezelimab continued to demonstrate manageable safety and sustained antitumor activity in pts with anti–PD-1–naive R/R cHL. These findings support further investigation of pembro + favezelimab.

©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.

Authors

Nathalie A. Johnson, David Lavie, Peter Borchmann, Gareth P. Gregory, Alex F. Herrera, Leonard Minuk, Vladan Vucinic, Philippe Armand, Abraham Avigdor, Robin Gasiorowski, Yair Herishanu, Colm Keane, John Kuruvilla, Rachel Marceau West, Pallavi Pillai, Rushdia Yusuf, John Timmerman