Lenalidomide and Epcoritamab for the Treatment of Previously Untreated Follicular Lymphoma

PRIMARY OBJECTIVE: I. To assess efficacy (complete response \[CR\] rate) of epcoritamab and lenalidomide (E-Len) in patients with de novo follicular lymphoma (FL). SECONDARY OBJECTIVES: I. To further assess efficacy of the combination (objective response rate \[ORR\], progression free survival \[PFS\], duration of response). II. To characterize the adverse event profile of the combination. EXPLORATORY OBJECTIVES: I. To characterize the T-cell population balance in patients treated with E-Len. II. To evaluate the predictive role of genetic mutations on durability of response to E-Len (including m7 Follicular Lymphoma International Prognostic Index \[FLIPI\] score). III. To evaluate minimal residual disease (MRD) dynamics on treatment. OUTLINE: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 of each cycle and epcoritamab subcutaneously (SC) on days 1, 8, 15, and 21 of cycles 1-3 and on day 1 of each subsequent cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may be re-treated with study treatment at any point during the follow-up period as long as they did not progress during treatment or stop due to unacceptable toxicity. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) as well as bone marrow biopsy throughout the trial. Patients undergo blood sample collection on trial and during follow-up. After completion of study treatment, patients are followed for safety on days 7, 30, and 60, for active response every 6 months for up to 2 years, and then for survival every 6 months.