Preliminary analysis of data evaluating investigational epcoritamab (DuoBody CD3xCD20) combination demonstrates 95% overall response rate in patients with previously untreated follicular lymphoma

A preliminary analysis of data from the EPCORE NHL-2 study (NCT04663347), evaluating epcoritamab in combination with rituximab-lenalidomide (R2), demonstrated an overall response rate (ORR) of 95% and complete response rate (CRR) of 85% in patients with previously untreated FL. The safety and efficacy for this use have not been established. The data were shared during a rapid oral presentation (Abstract #7014) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, IL and virtually, May 31-June 4, 2024.

Separately, new data from the cycle 1 optimization part (C1 OPT) of the EPCORE NHL-1 study (NCT03625037), evaluating epcoritamab in patients with relapsed/refractory (R/R) FL, showed that following additional mitigation strategies, cytokine release syndrome (CRS) (any grade) was reported in 49 percent of patients vs. 66 percent of patients (any grade) in the pivotal cohort. Additionally, there were no Grade 3 or higher CRS events and no reported immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS are adverse reactions, which can be serious and/or life threatening. Patients need to be monitored and carefully managed per current practice guidelines. These results (Abstract #7015) were selected to be a part of Best of ASCO (July 19-20 in Boston, MA), which features the most impactful research from the 2024 ASCO Annual Meeting.

FL is the second most common form of non-Hodgkin lymphoma (NHL), accounting for 20-30 percent of all NHL cases. About 15,000 people develop FL each year in the U.S. FL is considered incurable with current standard of care therapies and patients often relapse. With each subsequent line of therapy, patients receiving currently available treatments may experience shorter durability of remission.

EPCORE NHL-2 Results in First-Line FL (Abstract #7014): The EPCORE NHL-2 study analysis included results from two arms of the study. Arm 6 evaluated epcoritamab in combination with R2 in patients with previously untreated FL (n=41). With a median follow-up of 21.1 months, additional findings from this arm showed durable responses, with an estimated 89 percent of patients remaining progression free and 93 percent of patients who had achieved a CR remaining in CR at 18 months.

“The results from this preliminary analysis of epcoritamab in combination with rituximab-lenalidomide as a first-line, chemotherapy-free treatment for patients with FL are encouraging and support the continued evaluation of epcoritamab in this patient population,” said Joshua Brody, MD, Director, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine.

The most common treatment-emergent adverse events (TEAEs) in these first-line patients were COVID-19 (63 percent), CRS (56 percent) and neutropenia (56 percent). All CRS events were low grade (41 percent Grade 1 and 15 percent Grade 2) and resolved. Most CRS events occurred after patients received their first full dose of epcoritamab, and none led to treatment discontinuation. Two fatal TEAEs occurred due to COVID-19 pneumonia and septic shock.

The EPCORE NHL-2 study results also included the first data disclosure from arm 7, which evaluated epcoritamab administered every 8 weeks for patients with first- or second-line FL in CR or partial response (PR) following standard-of-care treatment (n=20). Median follow-up was 19.7 months. An estimated 90 percent of patients remained alive at 21 months. Notably, 100 percent of patients who entered the arm with a PR converted to a CR (n=8). In arm 7, the most common TEAEs were COVID-19 (70 percent) and CRS (55 percent). Only one CRS event (Grade 1) occurred during Q8W maintenance dosing. All other CRS events were during cycle 1 (C1) step-up dosing, as expected for these patients who had not previously received epcoritamab. One fatal TEAE occurred related to respiratory failure caused by post-acute COVID syndrome.

EPCORE™ NHL-1 Data in Later-line FL (Abstract #7015): In this C1 optimization cohort in patients with R/R FL, patients received epcoritamab in 3 step-up doses (0.16, 0.8, and 3 mg), along with dexamethasone prophylaxis and hydration recommendations followed by full 48-mg doses until disease progression or unacceptable toxicity. There was no mandatory hospitalization. With a median follow-up of 5.7 months, CRS rate was 49% (Grade 1 40%, Grade 2 9%), primarily occurring during cycle 1, and all events resolved. CRS was adequately identified in the outpatient setting and appropriately treated. There were no ICANS events. These findings show that mitigation measures implemented early in the epcoritamab treatment cycle may lead to substantial improvements in the incidence and severity of CRS and ICANS. Further, among the 81 response-evaluable patients in the cohort, ORR was 91 percent and CR rate was 68 percent, suggesting that the additional CRS mitigation did not impact efficacy.

On February 26, 2024, the FDA granted Priority Review for the supplemental Biologics License Application (sBLA) for epcoritamab-bysp for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. Use of epcoritamab in FL is not approved in the U.S. or in the EU or in any other territory. The safety and efficacy of epcoritamab for use in FL have not been established.