Comparison of Favezelimab/Pembrolizumab (MK-4280A) Therapy with Standard Chemotherapy in Patients with Relapsed or Refractory Classic Hodgkin Lymphoma Following PD-(L)1 Therapy

Classical Hodgkin lymphoma (cHL) is a malignant disease of the lymphatic system in which lymphocytes—a type of white blood cell that is part of the body’s immune system—become cancerous. The most common symptoms include swollen lymph nodes, fever, night sweats, weight loss, and itching. This type of cancer often affects young adults and is frequently treatable in its early stages. The exact causes are unclear, but genetic factors and infections such as the Epstein-Barr virus may play a role. Treatment depends on the stage and risk classification of the disease. Following treatment, imaging is performed using a PET-CT scan. If residual cancer cells are detected, additional radiation therapy is administered. If the disease recurs after this treatment, reinduction therapy is recommended, using, for example, DHAP (dexamethasone, cytarabine, and cisplatin), bendamustine, gemcitabine, or ICE (ifosfamide, carboplatin, and etoposide), along with high-dose chemotherapy followed by an autologous stem cell transplant.

The goal of this Phase 3 study is to investigate the efficacy and safety of therapy with Favezelimab and Pembrolizumab compared to standard chemotherapy in a larger number of patients. Both drugs are immunotherapies in the form of antibodies. Favezelimab blocks the LAG-3 protein, and pembrolizumab blocks the PD-1 protein. Both proteins normally inhibit the activity of the immune system. By blocking these proteins, the immune system is expected to fight cancer cells more effectively. Pembrolizumab is already approved for the treatment of cHL. Favezelimab has not yet been approved.

Participants in the study will be randomly assigned to 2 groups. Group 1 will receive the combination therapy of favezelimab and pembrolizumab as an infusion via a venous line. A total of up to 35 infusions will be administered at 3-week intervals. Group 2 will receive either chemotherapy with bendamustine as an infusion on days 1 and 2 of a 3- to 4-week cycle (for up to 6 cycles) or with gemcitabine as an infusion on days 1 and 8 of a 3-week cycle (for up to 6 cycles). The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Treatments and follow-up visits as part of the study will take place for up to approximately 3.5 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease progresses again during therapy. The study primarily investigates progression-free survival and overall survival.

Patients aged 18 and older with classical Hodgkin lymphoma are eligible to participate in this study. The disease must show a recurrence (relapse) or be uncontrollable (refractory) following PD-(L)1 inhibitor therapy, or be uncontrollable (refractory).