Evaluation of the Safety and Efficacy of Combination Therapy with Favezelimab and Pembrolizumab and the Respective Monotherapies in Hodgkin's and Non-Hodgkin's Lymphomas

Lymphomas are types of blood cancer that affect the lymphatic system. The lymphatic system is part of the immune system and helps fight infections. In Hodgkin lymphoma (cHL), certain cells—known as Reed-Sternberg cells—can be found; all other types of lymphoma are classified as non-Hodgkin lymphoma (NHL). NHL encompasses a wide variety of subtypes, including diffuse large B-cell lymphoma (DLBCL) and indolent non-Hodgkin lymphoma (iNHL), which is itself an umbrella term for several different types of lymphoma and indicates that these lymphomas have a less aggressive course. These include: follicular lymphoma and small lymphocytic lymphoma (SLL). SLL is closely related to chronic lymphocytic leukemia (CLL). Marginal zone lymphoma, lymphoplasmacytic lymphoma, and hairy cell leukemia. All lymphomas can cause symptoms such as swollen lymph nodes, fever, night sweats, and weight loss. The exact causes of lymphomas are unknown, but genetic mutations and a weakened immune system play a role. Standard treatment may include chemotherapy, radiation therapy, and immunotherapy approaches. Pembrolizumab is an established immunotherapy drug that blocks the PD-1 receptor, thereby activating the body’s immune system to fight cancer cells; it is already approved. Favezelimab is a new experimental antibody that targets the so-called LAG-3 protein to further enhance the immune response.

The MK-4280-003 study will first determine the optimal dose of favezelimab in combination with pembrolizumab (1 treatment cycle of 21 days) in Phase 1, and will then evaluate the efficacy of the drug combination in Phase 2. For the first phase, participants will be assigned to 3 groups in an open-label, non-randomized manner; each group will receive a different dose of Favezelimab. Treatment will be administered to all patients in 3-week cycles for up to two years. For this second phase, there are 5 groups, divided according to diagnosis (1 group for DLBCL, 3 groups for cHL, 1 group for iNHL). All participants receive combination therapy with Favezelimab and Pembrolizumab; only two of the cHL groups receive just one of the two drugs alone (Pembrolizumab or Favezelimab), and this assignment is random. After treatment, the study will primarily compare the side effects that occur and the response rates.

To participate in the study, patients must be at least 18 years old and have Hodgkin lymphoma (cHL), DLBCL, or indolent non-Hodgkin lymphoma (iNHL). In addition, they must have measurable tumors from which a tissue sample will be taken during the course of the study to test for specific tumor markers.