A phase 1/2 study of favezelimab in combination with pembrolizumab for anti–PD-1–naive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL): An updated analysis.
Authors: John Timmerman, David Lavie, Borchmann Peter, Gareth P. Gregory, Alex Francisco Herrera, Leonard Minuk, Vladan Vucinic, Philippe Armand, Abraham Avigdor, Robin Gasiorowski, Yair Herishanu, Colm Keane, John Kuruvilla, Rachel Marceau West, Pallavi Pillai, Patricia Marinello, Nathalie A. Johnson
Journal: Journal of Clinical Oncology (2024)

7055 Background: PD-1 inhibitors such as pembrolizumab are an important treatment option for patients (pts) with R/R cHL, but treatment failure remains a significant challenge. Dual immune checkpoint blockade with a PD-1 inhibitor and a lymphocyte-activation gene 3 (LAG-3) inhibitor shows promise as a treatment option for R/R cHL. In a multicohort phase 1/2 study (NCT03598608) evaluating the anti–LAG-3 monoclonal antibody favezelimab in combination with pembrolizumab for R/R hematologic malignancies, pembrolizumab plus favezelimab demonstrated sustained antitumor activity and acceptable safety in the cohort of pts with anti–PD-1–naive R/R cHL (cohort 1). We present updated results from this cohort after additional follow-up. Methods: Eligible pts were aged ≥18 years with R/R cHL; prior treatment with or ineligibility for autologous stem cell transplantation or no response to salvage chemotherapy; no prior PD-1 inhibitor; and an ECOG PS of 0 or 1. The study comprised a safety lead-in (pembrolizumab 200 mg IV Q3W plus favezelimab 200-mg starting dose, then dose escalation to 800 mg IV Q3W using a modified toxicity probability interval method) and a dose expansion phase (pembrolizumab 200 mg Q3W plus favezelimab at the established recommended phase 2 dose of 800 mg Q3W for up to 35 cycles). Primary end point was safety. Objective response rate (ORR) per IWG 2007 criteria by investigator review was a secondary end point. Duration of response (DOR) and progression-free survival (PFS) per IWG 2007 criteria by investigator review and overall survival (OS) were exploratory. Results: Cohort 1 enrolled 30 pts. The median time from first dose to data cutoff (August 15, 2023) was 36.9 months (range, 29.4-48.6). Treatment-related adverse events (AEs) occurred in 27 pts (90%), of which the most common (≥20%) were hypothyroidism (27%), infusion-related reaction (23%), and fatigue (20%). Grade 3 or 4 treatment-related AEs occurred in 7 pts (23%). Five pts (17%) discontinued treatment due to treatment-related AEs. No deaths due to treatment-related AEs were reported. AEs of clinical interest occurred in 20 pts (67%); 3 pts (10%) had grade 3 events (colitis, pneumonitis, severe skin reaction) and 1 pt (3%) had a grade 4 event (hepatitis). The ORR was 83% (n = 25; 95% CI, 65-94); 11 pts (37%) had a complete response and 14 (47%) had a partial response. Median DOR was 17.0 months (range, 2.6-30.5), and an estimated 47% of responders remained in response at 24 months. Median PFS was 19.4 months (95% CI, 9.5-28.5), and the 24-month PFS rate was 46%. Median OS was not reached (NR; 95% CI, NR-NR), and the 24-month OS rate was 93%. Conclusions: With additional follow-up, favezelimab plus pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in pts with anti–PD-1–naive R/R cHL. Further studies to investigate this combination are warranted. Clinical trial information: NCT03598608 .