Background: Anti–PD-1 therapies such as pembro are a standard-of-care option for R/R cHL, but effective treatments for pts with disease progression on or after anti–PD-1–based therapy are limited. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory checkpoint receptor thought to contribute to anti–PD-1 resistance. In a phase 1/2 study, combination therapy with the humanized IgG4 anti–LAG3 antibody favezelimab + pembro demonstrated manageable safety and promising antitumor activity in pts with R/R cHL whose disease had progressed after anti–PD-1 therapy. The randomized, open-label, phase 3 KEYFORM-008 study (NCT05508867) will evaluate efficacy and safety of a coformulated favezelimab/pembro in pts with anti–PD-1–refractory R/R cHL.
Methods: Eligible pts are ≥18 yrs old with histologically confirmed R/R cHL who have progressed on anti–PD-1–based therapy and exhausted all other available treatment options with known clinical benefit and are ineligible for or failed autologous stem cell transplantation (ASCT). Pts must also have been ineligible for brentuximab vedotin (BV), relapsed on or whose disease failed to respond to BV, or discontinued BV due to toxicity. Approximately 360 pts will be enrolled and randomly assigned 1:1 to receive coformulated favezelimab 800 mg/pembrolizumab 200 mg IV Q3W or physician’s choice of chemo (gemcitabine, 800-1200 mg/m2 IV or bendamustine, 90-120 mg/m2 IV). Randomization will be stratified by prior ASCT (yes vs no) and ECOG PS (0 or 1 vs 2). Treatment will continue for ≤35 cycles of coformulated favezelimab/pembro or ≤6 cycles for chemo or until progressive disease (PD), unacceptable toxicity, or withdrawal. Pts in the chemo with PD confirmed by BICR per Lugano criteria may be eligible to cross over to coformulated favezelimab/pembrolizumab. Primary end point is PFS by BICR per Lugano criteria. Secondary end points are OS, ORR and DOR by BICR per Lugano criteria, and safety. Exploratory end points include PFS on subsequent anticancer therapy and HRQoL.
Results: Recruitment is ongoing at sites in Asia, Australia, Europe and North and South America.
Conclusion: Results of KEYFORM-008 will provide clarity on the efficacy and safety of coformulated favezelimab/pembro versus chemo in pts with anti–PD-1–refractory R/R cHL.
©2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.
David Lavie, John Timmerman, Ramón García-Sanz, Won-Seog Kim, Tae Min Kim, Abraham Avigdor, Daan Dierickx, Deepa Jagadeesh, Daniel Molin, Muhit Ozcan, Omur Gokmen Sevindik, Hayder Saeed, Yulia Sidi, Pallavi Pillai, Rushdia Yusuf, Alex F. Herrera