Background and Significance:

Although remarkable progress has been made in the understanding of the pathobiology of follicular lymphoma (FL) leading to the development of new targeted and immunotherapies, it remains an incurable disease, characterized by disease recurrence and risk of histological transformation. Response to induction chemoimmunotherapy is one of the most important prognostic factors. There is evidence from multiple studies suggesting that achieving a complete response (CR) by FDG-PET after induction therapy is prognostic for outcomes, including progression-free survival (PFS) and overall survival (OS).

Epcoritamab is a fully humanized CD20xCD3 T-cell-engaging bispecific antibody that redirects T cells to eliminate B cells and has shown promising activity in B-cell non-Hodgkin Lymphomas in several pivotal trials leading to the regulatory approval in relapsed diffuse large B cell lymphoma and FL after 2 or more prior lines of therapy.

Study Design:

This is a single arm, multicenter, open label trial phase II study (NCT06510361) investigating the efficacy of epcoritamab in patients (pts) who fail to achieve a CR after frontline chemoimmunotherapy.

Eligibility criteria include pts with biopsy-confirmed (fresh or archival tissue) FL grade 1-3A with measurable disease, 1 prior line with at least 3 cycles of systemic first-line therapy consisting of anti-CD20 antibody (e.g. obinutuzumab or rituximab) combined with chemotherapy (e.g. bendamustine, CHOP, CVP, or lenalidomide), an Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Exclusion criteria include include known or suspected CNS involvement or leptomeningeal disease, current uncontrolled CNS disease (including stroke, epilepsy, or CNS vasculitis) and progressive disease after front line therapy.

Epcoritamab (E) therapy, administered at a dose of 48 mg subcutaneously over 28 days cycles for 12 total cycles. In cycle 1, epcoritamab will be given with step-up consisting of a priming dose of 0.16 mg (day 1), intermediate dose of 0.8 mg (day 8), second intermediate dose of 3mg (day 15), and full dose of 48 mg (day 22 onward). C1-3 epcoritamab will be given weekly and C4-9 is bi-weekly and 10+ once every 4 weeks.

The primary objective is to assess theproportion of pts who achieve a complete remission (CR) as best response following treatment with epcoritamab. A CR rate of 25% will be undesirable and 50% will be considered desirable (alpha 0.05 and power of 90%). Secondary objectives include overall survival, objective response rate, duration of response, and duration of CR, and progression free survival. Response will be determined according to the Lugano criteria (Cheson et al. J Clin Oncol 2014). As exploratory objectives we will evaluate the serial single cell RNA to gauge changes in immune repertoire triggered by the bispecific expansion of immune cells and serial circulating tumor DNA for minimal residual disease detection and clonal evolution.

An estimated 3 academic US centers will enroll a total of 35 patients starting in mid-August 2024.

Disclosures

von Keudell:AbbVie: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy; Merck: Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria. Arnason:BMS: Other: Speaker fees; Regeneron Pharmaceuticals, Inc.: Other: Speaker fees. Advani:BeiGene: Honoraria, Other: DSMB/Advisory Boards, Research Funding; ADCT: Honoraria, Other: DSMB/Advisory Boards; Merck: Other: Steering committee, DSMB/Advisory Boards, Research Funding; Gilead: Research Funding; Autolus: Honoraria, Other: DSMB/Advisory Boards; Regeneron: Research Funding; Cyteir: Research Funding; Seattle Genetics: Research Funding; Roche/Genentech: Honoraria, Other: Steering committee, DSMB/Advisory Boards, Research Funding.

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2024
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