KEYFORM-008: Coformulated favezelimab and pembrolizumab (MK4280A) versus chemotherapy in relapsed/refractory classical Hodgkin lymphoma.

Abstract

TPS7585 Background: PD-1 inhibitors are highly effective in patients (pts) with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), but treatment options are limited for pts who have progressed after PD1 blockade. There is an unmet need for effective therapies for anti-PD1 resistant cHL. Upregulation of lymphocyte-activation gene 3 (LAG-3) expression in cHL is proposed to contribute to anti PD-1 resistance (Veldman J et al. Cancer Treat Rev. 2020; 82:101931). The anti–LAG3 antibody favezelimab plus the anti-PD-1 therapy pembrolizumab, has shown promising antitumor activity and manageable safety in pts with R/R cHL after anti-PD1 therapy (Timmerman J et al. Blood 2022; 140). In this ongoing trial, we evaluate the efficacy and safety of MK-4280A in pts with R/R cHL that are refractory to anti-PD1 therapy (ClinicalTrials.gov, NCT05508867). Methods: This randomized, open-label, parallel group, active-controlled phase 3 trial will enroll approximately 360 pts aged ≥ 18 years. Eligible pts will have histologically confirmed R/R cHL, which has progressed on anti-PD-1 mAb and have exhausted all available treatment options with clinical benefit including ineligibility for or failed auto-SCT. In addition, pts must have relapsed after treatment with or failed to respond to brentuximab vedotin (BV), were ineligible for BV or discontinued BV due to toxicity, have ECOG performance status (PS) 0-2, adequate organ function, and availability of archival or newly obtained tissue sample. Pts will be randomized 1:1 to receive MK-4280A (coformulated favezelimab 800 mg/pembrolizumab 200 mg; Arm A) IV Q3W or physician’s choice of gemcitabine (800-1200 mg/m2) IV or bendamustine (90-120 mg/m2) IV (Arm B). Randomization will be stratified by prior auto-SCT (yes vs no), and ECOG PS (0/1 vs 2). Treatment will continue for up to 35 cycles of MK-4280A, or until unacceptable toxicity, disease progression (PD), or withdrawal from trial. Pts in Arm B with PD confirmed by blinded independent central review (BICR) per Lugano criteria may be eligible to crossover to receive up to 35 cycles of MK-4280A. Disease response assessments by PET and CT or MRI will be performed Q12W during the trial. The primary endpoint is progression free survival (PFS) by BICR per Lugano criteria. Secondary endpoints are overall survival (OS), objective response rate (ORR) and duration of response (DOR) (by BICR per Lugano criteria), and safety. Exploratory endpoints include PFS on subsequent oncologic therapy, and pt reported quality of life. Adverse events will be monitored throughout the trial and graded per NCI CTCAE v5.0. PFS, OS and DOR will be estimated using Kaplan-Meier method. ORR with 95% CI will be estimated using the Clopper-Pearson method. Efficacy will be assessed in the intention-to-treat population and safety assessed in all treated pts. Enrollment in this trial is ongoing. Clinical trial information: NCT05508867 .