P1065: UPDATED RESULTS FROM AN OPEN-LABEL PHASE 1/2 STUDY OF FAVEZELIMAB IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH ANTI–PD-1–NAIVE RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA

Topic: 17. Hodgkin lymphoma - Clinical Background: Programmed death 1 (PD-1) inhibitors play a key role in treating relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), but improved treatment response remains an important clinical objective. Lymphocyte-activation gene 3 (LAG-3) downregulates T-cell activity and is commonly coexpressed with PD-1 on anergic T cells. Dual PD-1 and LAG-3 blockade has demonstrated antitumor activity, leading to FDA approval for unresectable or metastatic melanoma. Favezelimab (anti–LAG-3) is being investigated in combination with pembrolizumab (anti–PD-1) in a multicohort phase 1/2 efficacy and safety study (NCT03598608) in patients with R/R hematologic malignancies. Initial results demonstrated that pembrolizumab 200 mg and favezelimab 800 mg Q3W exhibited promising antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL (cohort 1; Johnson NA et al. J Clin Oncol. 2022;40(16 suppl):7516). Aims: Evaluate efficacy and safety of favezelimab + pembrolizumab in anti-PD-1–naive patients 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). Patients in cohort 1 had R/R cHL after autologous stem cell transplantation (ASCT) (or were ineligible for ASCT), or did not respond to salvage chemotherapy, and had no prior anti–PD-1 therapy. Part 1 included patients from all cohorts who received pembrolizumab 200 mg IV Q3W and favezelimab at a starting dose of 200 mg, escalating to 800 mg IV Q3W using a modified toxicity probability interval method. In part 2, patients received pembrolizumab 200 mg Q3W plus favezelimab at the established RP2D (800 mg Q3W) for ≤35 cycles (~2 years). Primary end points were safety and RP2D. Objective response rate (ORR) was a secondary end point. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Results: Thirty patients were enrolled in cohort 1. Median age was 40.5 years, 53% had an ECOG PS of 0, and 80% had ≤3 prior lines of therapy. At data cutoff (August 31, 2022), 10 patients (33%) had completed 2 years of study treatment, 14 patients (47%) had discontinued (9 progressive disease; 4 adverse events; 1 nonadherence to study drug regimen), and 6 (20%) had treatment ongoing. After a 25.5-month median follow-up (first dose to data cutoff; range, 18.0-37.2), 24 patients had objective response (ORR, 80% [95% CI, 61-92]; 10 [33%] complete responses, 14 [47%] partial responses). 29 patients (97%) had reduction in target lesion size from baseline and 25 (83%) had ≥50% reduction from baseline. Median DOR was 25.6 months (range, 0.0+ to 28.8+); an estimated 54% of responders remained in response ≥15 months. Median PFS was 19.4 months (95% CI, 9.0-28.5); 15-month PFS rate was 53%. Median OS was not reached (95% CI, NR-NR); 15-month OS rate was 93%. Among 26 patients (87%) with treatment related AEs, most common (≥15%) were hypothyroidism (27%); infusion-related reaction (23%); fatigue (20%); pruritus and headache (17% each). Grade 3/4 treatment related AEs occurred in 7 patients (23%). No deaths were treatment related. Of 3 patients who received hematopoietic stem cell transplantation after completion of study treatment, 1 had a grade 3/4 AE unrelated to study treatment (increased blood bilirubin) that resolved. Summary/Conclusion: Favezelimab + pembrolizumab continued to demonstrate sustained antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL. Further studies comparing this combination with pembrolizumab alone would be beneficial. Keywords: Clinical trial, Hodgkin’s lymphoma, Immunotherapy

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