Epcoritamab Elicits an ORR of 82% in Relapsed/Refractory Follicular Lymphoma

Epcoritamab-bysp (Epkinly) elicited a confirmed overall response rate (ORR) of 82% by independent review committee assessment in patients with relapsed or refractory follicular lymphoma who received 2 or more prior systemic treatments, which exceeded the prespecified threshold for efficacy in the phase 1/2 EPCORE NHL-1 trial (NCT03625037).¹

Additional topline data from the follicular lymphoma cohort (n = 128) showed that the median duration of response (DOR) with the T-cell–engaging bispecific antibody was not yet reached. Notably, 70.3% of these patients were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent. Moreover, no new safety signals were reported.

Cytokine release syndrome (CRS) represented the most common treatment-emergent toxicity, occurring in 66.4% of patients, with 1.6% of cases higher than grade 2 in severity. The optimization part of EPCORE NHL-1, which aligns with the FDA’s Project Optimus, continues to examine alternative step-up dosing regimens that could mitigate the risk of this adverse effect (AE). In a news release, Genmab A/S reported that early data on initial participants indicate a meaningful improvement in CRS.

Data from the follicular lymphoma cohort and the rest of the optimization portion of the research will be submitted for presentation at an upcoming medical meeting, and the company also shared plans to discuss with global regulatory authorities.

“These topline results are encouraging for [patients with] relapsed or refractory follicular lymphoma who are in need of new therapeutic options,” Jan van de Winkel, PhD, chief executive officer of Genmab A/S, stated in a press release. “With our partner AbbVie, we are committed to evaluating epcoritamab as a potential core therapy across B-cell malignancies.”

The open-label, multicenter trial is comprised of 3 parts: dose-escalation (phase 1), expansion (phase 2), and dose optimization (phase 2a).¹ Overall, the trial enrolled patients with relapsed or refractory CD20-positive mature B-cell non-Hodgkin lymphoma (B-NHL), which included follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma.²

Patients were required to have received at least 2 prior lines of antineoplastic therapy, including at least 1 anti-CD20 monoclonal antibody, measurable disease, and an ECOG performance status of 0 to 2.

The expansion portion of the research enrolled 3 cohorts of patients with different types of B-NHL in need for additional treatment options.¹

Previous data from the large B-cell lymphoma (LBCL) cohort (n = 157), which included those with DLBCL, HGBCL, PMBCL, and follicular lymphoma grade 3B, were presented at the 2022 EHA Congress.³

These patients received epcoritamab at the recommended phase 2 dose of 48 mg weekly, subcutaneously, in cycles 1 to 3, biweekly for cycles 4 to 9, and 4 times per week for cycles 10 and beyond. Administration continued until intolerable toxicity or progressive disease. For the first full dose, investigators required inpatient monitoring for 24 hours.

In this group, epcoritamab elicited an ORR of 63% (95% CI, 55%-71%) in this population, which included a 39% (95% CI, 31%-47%) complete response (CR) rate. Moreover, 3% of patients had stable disease and 24% had progressive disease. Responses proved to be consistent spanning key subgroups. Specifically, patients had an ORR of at least 46% irrespective of age, histology, exposure to CAR T-cell therapy, or number or prior lines of treatment.

With a median follow-up of 10.7 months (range, 0.3-17.9), the overall median DOR was 12.0 months (range, 0+ to 15.5+), and the median time to response was 1.4 months (range, 1.0-8.4). The median DOR for those who achieved a CR was not yet reached (NR), and the median time to CR was 2.7 months (range, 1.2-11.1).

At the time of presentation, the overall median progression-free survival (PFS) was 4.4 months (95% CI, 3.0-7.9), with a 6-month PFS rate of 43.9% (95% CI, 35.7%-51.7%). The median PFS for those who achieved a CR was NR, with 89% of these patients remaining in CR at 9 months. Additionally, the median overall survival (OS) was NR. The 6-month OS rate was 70.6% (95% CI, 62.7%-77.2%) and the 12-month OS rate was 56.9% (95% CI, 47.3%-65.4%) with the agent.

Safety data in this group showed that the most common any-grade AEs were CRS (49.6%), neutropenia (28%), pyrexia (23.5%), and fatigue (22.9%). Immune effector cell–associated neurotoxicity syndrome of any grade was reported in 10 patients; 9 cases were grade 1 or 2 and resolved, but 1 patient had a grade 5 case. Regarding CRS, 31.8%, 15.3%, and 2.5% of patients, respectively, had grade 1, 2, and 3 events. The median time to onset from the first full dose of epcoritamab was 20 hours, and this resolved in most (98.7%) of patients.

In May 2023, the FDA approved epcoritamab for use in adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from indolent lymphoma, and HGBCL, after 2 or more lines of systemic therapy.⁴ The accelerated approval was supported by findings from EPCORE NHL-1.

References

1. Genmab and AbbVie announce positive topline results from phase 1/2 EPCORE NHL-1 trial evaluating epcoritamab (DuoBody CD3xCD20) in patients with relapsed/refractory follicular lymphoma (FL). News release. Genmab A/S. June 28, 2023. Accessed June 28, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-and-abbvie-announce-positive-topline-results-phase-12
2. First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE NHL-1). ClinicalTrials.gov. Updated June 28, 2023. Accessed June 28, 2023. https://clinicaltrials.gov/study/NCT03625037
3. Thieblemont C, Phillips T, Ghesquieres H, et al. Primary results of subcutaneous epcoritamab dose expansion in patients with relapsed or refractory large B-cell lymphoma: a phase 2 study. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract LB2364.
4. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. FDA. May 19, 2023. Accessed June 28, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell