EPCORE FL-2: Phase 3 Trial of Epcoritamab with Rituximab and Lenalidomide (R2) Vs Chemoimmunotherapy or R2 in Previously Untreated Follicular Lymphoma.

TPS7084 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Most patients with advanced-stage FL in need of systemic therapy are treated with an anti-CD20 monoclonal antibody (eg, rituximab [R] or obinutuzumab [G]) with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or bendamustine [benda]). Recent studies have shown R plus lenalidomide (R2) is a potent FL treatment in the 1L and relapsed or refractory (R/R) settings and is a promising backbone for combination therapies. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, received breakthrough therapy designation by the FDA for R/R FL after ≥2 lines of systemic therapy. In the phase 1/2 trial (NCT04663347), epcoritamab plus R2 demonstrated high complete response (CR) rates in the 1L and R/R settings. The objective of this trial is to evaluate the safety and efficacy of 1L epcoritamab plus R2 vs CIT in patients with FL. Methods: EPCORE FL-2 (NCT06191744) is a global, randomized, open-label phase 3 trial. Eligible adult patients must have CD20+ histologically confirmed classic FL (previously grade 1–3A), stage III or IV disease (or bulky stage II), and in need of systemic treatment by meeting GELF criteria. Approximately 1080 patients will be randomized to 3 treatment arms (Table). Patients achieving CR or PR upon 6 cycles will move to epcoritamab on day 1 of cycles 7–12 (28-day cycles) and 13–21 (56-day cycles). After 120 weeks of treatment, patients will be followed for progression and survival. Dual primary endpoints will be CR rate at 30 months and progression-free survival in arm A vs arm B. Key secondary efficacy endpoints include overall survival, minimal residual disease negativity, and changes in patient-reported outcomes on the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire from baseline to week 25. Safety endpoints include incidence and severity of adverse events (AEs), including AEs of special interest (cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). The study is open for enrollment. Clinical trial information: NCT06191744 . [Table: see text]