Favezelimab and Pembrolizumab Show Survival Benefit in Relapsed Hodgkin Lymphoma
Favezelimab combined with pembrolizumab demonstrated a significant progression-free survival (PFS) benefit compared to chemotherapy in patients with relapsed or refractory classic Hodgkin lymphoma (cHL), according to findings from the phase 2 KEYFORM-008 trial presented at the 2026 European Hematology Association (EHA) Congress. While the investigational regimen extended the time until disease progression, chemotherapy produced a higher objective response rate (ORR) in the study population.
How did the treatment arms compare in the KEYFORM-008 trial?
The study, which randomized 203 patients, found that those receiving the LAG-3 inhibitor favezelimab plus the PD-1 inhibitor pembrolizumab achieved a median PFS of 6.4 months. In contrast, patients treated with physician-choice chemotherapy reached a median PFS of 5.7 months. Lead investigator Guilherme Fleury Perini, MD, of the Hospital Israelita Albert Einstein, reported a hazard ratio of 0.757 (P = .0462), indicating a statistically significant advantage for the combination therapy.
Despite the PFS benefit, chemotherapy resulted in a higher ORR of 67.7% compared to 44.2% for the favezelimab/pembrolizumab arm. The complete remission rate also favored chemotherapy at 36.4%, versus 13.5% for the investigational regimen. However, the duration of response (DOR) was notably longer with the combination therapy, with a median of 11.0 months compared to 5.4 months for chemotherapy.
Which patient subgroups benefited most from LAG-3 inhibition?
Subgroup analysis revealed that the combination regimen provided the strongest clinical benefit to specific patient populations. Patients who had previously undergone autologous stem cell transplantation (ASCT) saw a hazard ratio of 0.54. Additionally, patients under the age of 65 experienced a hazard ratio of 0.68. The most pronounced effect was observed in patients who had not received PD-1 inhibition as their most recent line of therapy, where the hazard ratio reached 0.50.
What happens next for the favezelimab clinical program?
Following the presentation of these findings, investigators stopped the KEYFORM-008 trial. According to Dr. Perini, the sponsor decided to terminate the entire clinical development program for favezelimab. This decision means that while the trial met its primary end point, further investigation of this specific LAG-3 and PD-1 combination within this development framework will not continue.
Safety profile of the investigational regimen
The safety data showed distinct differences between the two treatment approaches. The most frequent treatment-related adverse event (TRAE) in the favezelimab/pembrolizumab arm was hypothyroidism, affecting 15.4% of patients. In the chemotherapy group, common issues included nausea at 39.2%, anemia at 25.8%, and fatigue at 17.5%. Grade 3 or 4 toxicities in the chemotherapy arm were largely driven by hematologic events, specifically decreases in neutrophil and lymphocyte counts.
Frequently Asked Questions
What is the primary difference between the two study arms?
The favezelimab/pembrolizumab arm showed a longer time before disease progression (PFS) and a longer duration of response (DOR), while the chemotherapy arm showed a higher percentage of patients achieving a tumor response (ORR) and complete remission.
Why was the KEYFORM-008 trial stopped?
The trial was discontinued because the sponsor decided to terminate the entire clinical development program for the drug favezelimab.
How was the study population defined?
Participants were aged 18 or older with classic Hodgkin lymphoma that was refractory to PD-1 therapy, meaning their disease progressed within 12 weeks of their last anti–PD-1 treatment.
What were the most common side effects of the combination therapy?
Hypothyroidism was the most common event, reported in 15.4% of patients receiving the combination of favezelimab and pembrolizumab.
***
*Are you interested in the latest advancements in hematologic oncology? Subscribe to our newsletter for updates on emerging therapies and clinical trial results.*
