Genmab A/S announced new efficacy and safety data from two ongoing Phase 1/2 clinical trials evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, in adult patients with certain types of follicular lymphoma (FL). 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% of patients vs. 66% 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?s lymphoma (NHL), accounting for 20%-30% of all NHL cases.i About 15,000 people develop FL each year in the U.S.ii FL is considered incurable with current standard of care therapies and patients often relapse.iii,iv With each subsequent line of therapy, patients receiving currently available treatments may experience shorter durability of remission.v 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% of patients remaining progression free and 93% of patients who had achieved a CR remaining in CR at 18 months.

The most common treatment-emergent adverse events (TEAEs) in these first-line patients were COVID-19 (63%), CRS (56%) and neutropenia (56%). All CRS events were low grade (41% Grade 1 and 15% 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% of patients remained alive at 21 months. Notably, 100% 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%) and CRS (55%).

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.

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% and CR rate was 68%, suggesting that the additional CRS mitigation did not impact efficacy. EPCORE? NHL-2 is a phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, and preliminary efficacy of epcoritamab in combination with standard of care agents in patients with B-cell non-Hodgkin?s lymphoma, including FL, and across multiple lines of therapy.

The trial consists of two parts ? Part 1 (dose escalation) and Part 2 (dose expansion) ? and 10 different treatment arms. The primary objective of Part 1 is safety, and it includes arm 1-5 and arm 10.

Part 2 includes all 10 arms (arm 1-10) with the objective of preliminary efficacy. However, the primary objective of arm 7 is safety. EPCORE?

NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin?s lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options and generated pivotal data for patients with FL and diffuse large B-cell lymphoma (DLBCL).

The optimization part evaluated additional cytokine release syndrome (CRS) mitigation strategies during cycle 1. The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints.