Epcoritamab Gains Japanese Approval for R/R Follicular Lymphoma

The Ministry of Health, Labour, and Welfare in Japan has approved epcoritamab (Epkinly) for the treatment of patients with relapsed or refractory grade 1 to 3A follicular lymphoma who have received 2 or more prior lines of therapy.1

The regulatory decision was supported by data from the phase 1/2 EPCORE NHL-1 (NCT03625037) and EPCORE NHL-3 (NCT04542824) clinical trials.

“In the treatment of follicular lymphoma, where options become limited with each relapse, there remains a high unmet need for third-line and subsequent therapies in the absence of a clear standard of care,” Koji Izutsu, MD, head of the Department of Hematology at National Cancer Center Hospital in Tokyo, Japan, stated in a news release. “The responses and tolerability demonstrated in [EPCORE NHL-3] support the potential of epcoritamab to become an important option in future treatment strategies for relapsed/refractory follicular lymphoma.”

In the global EPCORE NHL-1 trial, evaluable patients with relapsed/refractory follicular lymphoma (n = 128) achieved an overall response rate (ORR) of 82% (95% CI, 74.3%-88.3%), with a complete response (CR) rate of 62.5%. Of the patients evaluable for minimal residual disease (MRD) analysis (n = 91), 67% achieved MRD negativity. Additionally, more than half of responding patients remained in response at a median follow-up of 14.8 months; the median duration of response (DOR) was not yet reached.

Among patients treated with the 2-step step-up dosing (SUD) regimen (n = 128), treatment-emergent adverse effects (TEAEs) were reported in 93% of patients. The most common were cytokine release syndrome (CRS; 66.4%) and injection site reactions (36.7%).

In the Japanese EPCORE NHL-3 trial, evaluable patients with relapsed/refractory follicular lymphoma (n = 21) experienced an ORR of 95.2% (95% CI, 76.2%-99.9%) with a CR rate of 76.2% at a median follow-up of 21.2 months. MRD negativity was achieved by 88.9% of evaluable patients (n = 18).

TEAEs observed in patients receiving the 2-step SUD regimen included CRS (90.5%), injection site reactions (71.4%), rash (28.6%), neutropenia (28.6%), increased alanine aminotransferase levels (23.8%), and increased aspartate aminotransferase levels (23.8%).1

“Patients living with relapsed or refractory follicular lymphoma in Japan deserve options, and we are proud that [epcoritamab] may help treat patients as their cancer returns or stops responding to other therapies,” Judith Klimovsky, MD, executive vice president and chief development officer of Genmab, added in a news release.

In June 2024, the FDA granted accelerated approval to epcoritamab-bysp for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.2

Study Design of EPCORE NHL-1

The open-label, multicenter, phase 1/2 EPCORE NHL-1 trial enrolled patients with relapsed or refractory follicular lymphoma who received at least 2 prior lines of systemic therapy, had an ECOG performance status of 0 to 2, and had measurable disease per Lugano criteria.1

The study included a dose-escalation phase, a dose-expansion phase, and a dose-optimization phase. In the expansion phase, additional patients were included to further evaluate the safety and efficacy of epcoritamab in three cohorts of patients with different subtypes of relapsed/refractory B-cell non-Hodgkin lymphoma including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). The optimization phase focused on evaluating CRS mitigation strategies during the first treatment cycle.1

The primary end point of the expansion phase was ORR as assessed by an independent review committee. Key secondary end points included DOR, CR rate, duration of CR (DOCR), progression-free survival (PFS), time to response per Lugano criteria, overall survival (OS), time to next therapy, and MRD-negativity rate.

The primary end point of the optimization phase was the rate of grade 2 or higher CRS and all-grade CRS events occurring from the first dose of epcoritamab through 7 days following administration of the second full dose.

Study Design of EPCORE NHL-3

A total of 36 Japanese patients with relapsed, progressive, or refractory mature B-cell non-Hodgkin lymphoma, including follicular lymphoma, were enrolled in the open-label, multicenter, phase 1/2 EPCORE NHL-3 trial. To participate, patients needed to have received prior therapy for B-cell non-Hodgkin lymphoma and have measurable disease per Lugano criteria. The trial was designed to evaluate the safety and efficacy of subcutaneous epcoritamab in this population.

Patients were enrolled into two parts: a phase 1 first-in-human dose escalation phase and a phase 2 expansion phase. In the phase 2 expansion phase, additional patients were included to further assess the efficacy of epcoritamab specifically in Japanese patients with relapsed or refractory disease.

The primary end point of the expansion phase was ORR as assessed by an independent review committee. Key secondary end points included DOR, CR rate, DOCR, PFS, and time to response per Lugano criteria.

References

1. Epkinly (epcoritamab) approved by Japan Ministry of Health, Labour and Welfare for additional indication as a treatment for relapsed or refractory follicular lymphoma. Genmab. February 20, 2025. Accessed February 20, 2025. https://ir.genmab.com/news-releases/news-release-details/epkinlyr-epcoritamab-approved-japan-ministry-health-labour-and
2. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. FDA. June 26, 2024. Accessed February 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma