Favezelimab plus pembrolizumab in anti–pd‐1–refractory classical hodgkin lymphoma (chl): estimating the relative efficacy of favezelimab

Introduction: There is an unmet need for effective therapeutic options for patients (pts) with relapsed or refractory (R/R) cHL whose disease has progressed after a PD-1 inhibitor. Favezelimab is a LAG-3 inhibitor that had tolerable safety and effective antitumor activity when used in combination with pembrolizumab in pts with anti–PD-1–refractory R/R cHL in the phase 1/2 MK-4280-003 study (Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). ORR in this study was promising, but the contribution of favezelimab is unclear. In this post hoc analysis, we assessed relative efficacy of favezelimab + pembrolizumab versus pembrolizumab alone in pts with anti–PD-1–refractory R/R cHL. Because there are no clinical trial data for pembrolizumab alone in this setting, we used historical data from pts with R/R cHL who received pembrolizumab beyond disease progression in the phase 2 KEYNOTE-087 study. Method: Pts from MK-4280-003 with a baseline and postbaseline scan were included. Pts from KEYNOTE-087 who received >2 doses of pembrolizumab beyond progression, had confirmed progression within 12 weeks of the last dose of pembrolizumab (confirmatory scan ≥4 weeks from initial progression), and had postprogression scans available, were included in the historical control arm. Pts in MK-4280-003 received pembrolizumab 200 mg IV Q3W plus favezelimab 200 mg or 800 mg IV Q3W. Pts in KEYNOTE-087 received pembrolizumab 200 mg IV Q3W. For pts in KEYNOTE-087, baseline tumor size was reset at first progression and best change in target lesion size was calculated in the postprogression period. ORR was assessed per Cheson 2007 criteria. A bootstrapping method compared change in target lesion size, with 1000 random samples averaged from pts in KEYNOTE-087. Results: 27 of 33 pts in MK-4280-003 were included for the radiographic analysis. In KEYNOTE-087, 123 pts developed disease progression on pembrolizumab, of whom 81 received postprogression pembrolizumab and were included in this analysis. ORR for pts who received favezelimab + pembrolizumab was 31% (range 15–51) compared with 2.5% (range 0–5.9) for pts who received potsprogression pembrolizumab. Average change from baseline in target lesion size was −46.6% for favezelimab + pembrolizumab compared with −0.37% for postprogression pembrolizumab. 44% of pts who received favezelimab + pembrolizumab had a ≥50% reduction in target lesion size compared with 5% of pts who received postprogression pembrolizumab. Results of the bootstrapping analysis showed a better response for favezelimab + pembrolizumab relative to pembrolizumab monotherapy in 99.4% (26,826 of 27,000) of samples. Keywords: Hodgkin lymphoma, immunotherapy 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. Conflicts of interests pertinent to the abstract P. Armand Consultant or advisory role: BMS, MSD, ADC Therapeutics, GenMab, Enterome, Tessa Therapeutics, Regeneron, Genentech/Roche, AstraZeneca, Xencor, ATB Therapeutics, Foresight Diagnostics Honoraria: Merck Research funding: MSD, BMS, Roche, Adaptive Biotechnologies, Affimed Therapeutics, Genentech, IGM, Kite--a Gilead company 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 J. Timmerman Consultant or advisory role: Kite/Gilead, DAVA Oncology, Oncovalent Therapeutics Honoraria: Kite/Gilead Research funding: BMS, Kite- A Gilead company, Merck Travel grants: BMS N. Johnson Consultant or advisory role: Roche, Merck, AbbVie, Gilead Honoraria: Roche, Merck D. Lavie Consultant or advisory role: AbbVie, Novartis, Takeda K. Thiagarajan Employment or leadership position: Vantage Research Inc. Consultant or advisory role: Vantage Research Inc. B. Topp Employment or leadership position: Merck Stock ownership: Merck P. Pillai Employment or leadership position: Merck Stock ownership: 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 Travel grants: BMS