An open‐label phase 1/2 study of favezelimab plus pembrolizumab in patients with relapsed/refractory classical Hodgkin lymphoma with/without previous anti‐PD‐1 treatment (2023)

Introduction: Dual blockade of PD-1 and lymphocyte-activation gene (LAG-3) has shown antitumor activity; however, the activity of the combination for patients (pts) with relapsed or refractory (R/R) classical Hodgkin’s lymphoma (cHL) is unclear. Initial results of a multicohort phase 1/2 study (NCT03598608) showed that the anti–PD-1 inhibitor pembrolizumab (200 mg Q3W) combined with the anti–LAG-3 inhibitor favezelimab (800 mg Q3W) showed promising antitumor activity and acceptable safety in pts with R/R cHL who either were anti–PD-1 naive (cohort 1) or had progression after anti–PD-1 therapy (cohort 2) (Johnson NA et al. J Clin Oncol. 2022;40(16 suppl):7516; Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). Updated data with additional follow-up from both cohorts are presented. Methods: Pts in cohorts 1 and 2 had R/R cHL after autologous stem cell transplant (ASCT) (or were ineligible for ASCT) or did not respond to salvage chemotherapy and had an ECOG PS of 0 or 1. Pts in cohort 1 had no prior anti–PD-1 therapy; pts in cohort 2 had progression within 12 weeks after ≥2 doses of anti–PD-1 therapy, per Cheson 2007 criteria. Pts 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. The secondary end point was ORR. DOR, PFS, and OS were exploratory. Results: At the data cutoff (Aug 31, 2022), median follow-up (range) was 25.5 (18.0–37.2) months and 29.3 (9.0–43.4) months in cohort 1 and cohort 2, respectively. Anti–PD-1 was the most recent therapy for 17 pts (50%) in cohort 2. In cohort 1, 47% (14 pts) of pts discontinued treatment, and 74% (25 pts) discontinued treatment in cohort 2. ORR was 80% in cohort 1 (95% CI, 61%–92%, 10 CR, 14 PR) and 29% in cohort 2 (95% CI, 15%–47%, 3 CR, 7 PR). Additional efficacy analyses are included in the Table. Treatment-related adverse events (AEs) occurred in 26 pts (87%) and 28 pts (82%) in cohorts 1 and 2, respectively. The most common treatment-related AEs were hypothyroidism (27%) in cohort 1 and hypothyroidism and nausea (18% each) in cohort 2. Grade 3/4 AEs occurred in 7 pts (23%) in cohort 1 and in 6 pts (18%) in cohort 2. No treatment-related deaths occurred. Conclusion: With additional follow-up, the combination of favezelimab plus pembrolizumab continued to show antitumor activity and manageable safety in anti–PD-1–naive pts with R/R cHL and in pts whose disease progressed after anti–PD-1 therapy. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Keywords: Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. D. Lavie Consultant or advisory role: AbbVie, Novartis, Takeda N. Johnson Consultant or advisory role: Roche, Merck, AbbVie, Gilead Honoraria: Roche, Merck A. F. Herrera Consultant or advisory role: BMS, Seattle Genetics, Merck, Genentech/Roche, AstraZeneca/MedImmune, Karyopharm Therapeutics, ADC Therapeutics, Takeda, Regeneron, Genmab, Tubulis GmbH, Pfizer, Adicet Bio, Caribou Biosciences, AbbVie Research funding: BMS, Merck, Genentech/Roche, Kite—a Gilead Company, AstraZeneca, Seattle Genetics, Gilead Sciences, ADC Therapeutics Educational grants: BMS A. Avigdor Consultant or advisory role: Takeda, Gilead, Novartis, Roche, BMS Educational grants: AbbVie R. Gasiorowski Honoraria: MSD, Otsuka, Novartis, Astellas, Janssen, AbbVie, Antengene G. Gregory Consultant or advisory role: Roche, Novartis, BMS, Janssen Honoraria: Roche, BMS Research funding: BeiGene, Merck, AbbVie, Janssen Educational grants: Roche, Novartis Other remuneration: Speaker Bureau—Roche; Expert Testimony—Janssen C. Keane Consultant or advisory role: Roche, Beigene, MSD V. Vucinic Consultant or advisory role: MSD, BMS Celgene, Novartis, Gilead Kite, Takeda Honoraria: Novartis, Gilead Kite, Takeda, MSD, BMS Celgene, AbbVie, Amgen Educational grants: Sobi, BMS, Celgene Y. Herishanu Honoraria: AbbVie, Janssen, Roche, Medison, Beigene C. Andreadis Research funding: Merck P. Armand Consultant or advisory role: BMS, MSD, ADC Therapeutics, GenMab, Enterome, Tessa Therapeutics, Regeneron, Genentech/Roche, AstraZeneca, Xencor, ATB Therapeutics, Foresight Diagnostics Research funding: MSD, BMS, Roche, Adaptive Biotechnologies, Affimed Therapeutics, Genentech, IGM, Kite—a Gilead company J. Kuruvilla Consultant or advisory role: AbbVie, Antengene, BMS, Gilead, Karyopharm, Medison Ventures, Merck, Roche, Seattle Genetics Honoraria: AbbVie, Amgen, Astra Zeneca, BMS, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics Research funding: Roche, AstraZeneca, Merck Other remuneration: Officer/Board of Directors—Lymphoma Canada; Data Safety Monitoring Board—Karyopharm P. L. Zinzani Consultant or advisory role: Celltrion, Gilead Sciences, Janssen-Cilag, BMS, SERVIER, Sandoz, MSD, Roche, EUSA Pharma, Kyowa Kirin, Takeda, Secure BIO, TG Therapeutics, Novartis, ADC Therapeutics, Incyte, BeiGene Other remuneration: Speaker Bureau—MSD, EUSA Pharma, Novartis R. Marceau West Employment or leadership position: Merck P. Pillai Employment or leadership position: Merck Sharpe and Dohme Stock ownership: Merck Sharpe and Dohme P. Marinello Employment or leadership position: Merck Stock ownership: Merck J. Timmerman Consultant or advisory role: Kite/Gilead, DAVA Oncology, Oncovalent Therapeutics Honoraria: Kite/Gilead Research funding: BMS, Kite – A Gilead Company, Merck Educational grants: BMS