New Epcoritamab Data Show Strong Results in B-Cell Lymphomas

Newly released data from the ongoing phase I/II EPCORE NHL-2 trial show the T-cell-engaging bispecific antibody epcoritamab (Epkinly) led to a high overall response rate and complete metabolic response rate when used in combination with rituximab (Rituxan) and lenalidomide (Revlimid) in patients with relapsed or refractory follicular lymphoma (R/R FL).¹

The new data were presented at the 2023 European Hematology Association (EHA) Congress held earlier this month in Frankfurt, Germany. The FL news was presented alongside updated data from the EPCORE NHL-1 expansion cohort, which showed the therapy led to deep and durable responses in patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) and high grade B-cell lymphoma (HGBCL).²

The drug’s developers, Genmab and AbbVie, also announced in a press release that they had dosed their first patients in the phase 3 EPCORE DLBCL-2 trial (NCT05578976) and the phase 2 EPCORE DLBCL-3 trial (NCT05660967), both of which will evaluate the safety and efficacy of the therapy as a first-line treatment in adults and elderly patients with DLBCL.³

Discussing the FL results, Anna Sureda, MD, PhD, of the University of Barcelona, and colleagues, explained that patients with FL are typically treated with chemoimmunotherapy, according to the release. However, about 1 in 5 patients experience progression within 24 months of their initial treatment, and early progression is a strong predictor of poor outcomes.

Epcoritamab, which is administered subcutaneously, demonstrated antitumor activity and a manageable safety profile as a single-agent in patients with R/R FL, the authors said, but it has also shown promise in combination therapies.

The newly released data report on a pooled analysis of the 2a and 2b cohorts from the ongoing phase I/II EPCORE NHL-2 trial. In the study, patients with CD20-positive R/R FL received epcoritamab plus rituximab and lenalidomide (R2) for 12 28-day cycles. The dosing schedule varied between the 2 cohorts.

Among 109 patients who received the therapy in the trial, the median age was 65 years. More than half (56%) had Follicular Lymphoma International Prognostic Index (FLIPI) scores of 3-5, and 61% had stage IV disease. Most (59%) had only one prior line of treatment. The vast majority (92%) had received alkylating agents, 62% had received anthracyclines, and 2 patients had previously received chimeric antigen receptor (CAR) T-cells.

The investigators reported an overall response rate (ORR) of 98%, and a complete metabolic response (CMR) rate of 87% among the 104 patients whose responses were evaluable.

Those findings held up across subgroups. Among patients with progression within 24 months after their initial therapy, the investigators found a 98% ORR and a 75% CMR rate. In patients who were refractory to both an anti-CD20 and an alkylating agent (double-refractory), the ORR was 95% and the CMR rate was 75.7%. In primary refractory patients—those with no response at 6 months or who relapsed within 6 months—the ORR was 100% and the CMR rate was 83.8%. In patients refractory to prior anti-CD20 therapy, the ORR was 96% and the CMR was achieved in 80.9%.

“The results being presented today are encouraging and warrant further evaluation of epcoritamab in combination with R2 in this patient population to determine if this combination could potentially be offered as a treatment option for patients in need of alternative therapeutic options,” Sureda said in a press release.

In terms of safety, the most common treatment-emergent adverse events were neutropenia (57%), cytokine release syndrome (CRS; 48%), injection-site reactions (41%), and fatigue (36%). Most of the cases of CRS were grade 1 or 2, and most occurred following the first dose. No patients discontinued treatment as a result of adverse events. Two patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), though both cases resolved.

In addition to the R/R FL data, investigators also presented updated data from the EPCORE NHL-1 large B-cell lymphoma (LBCL) expansion cohort. Like results published earlier this year, the new data showed epcoritamab led to deep and durable responses. At a median follow-up of 20 months, the new data showed an ORR of 63.1% and a complete response (CR) rate of 39.5% in patients with relapsed or refractory LBCL, and a 61.9% ORR and 39.6% CR rate in patients with relapsed or refractory DLBCL. The median overall survival times were 18.5 months and 19.4 months, respectively.

Judith Klimovsky, MD, the executive vice president and chief development officer at Genmab, said Genmab and Abbvie remain committed to evaluating the therapy.

“The data being presented at EHA demonstrate our shared commitment to development of epcoritamab as a potential core therapy for B-cell malignancies,” Klimovsky said.

References

1. Sureda A, Falchi L, Leppa S, et al. Epcoritamab with rituximab + lenalidomide (R2) provides durable responses in patients with high-risk follicular lymphoma, regardless of POD24 status. Abstract presented at: European Hematology Association 2023 Congress; June 8-11, 2023; Frankfurt, Germany. Abstract S222.

2. Jurczak W, Ghesquieres, Karimi Y, et al. Longer follow-up from the pivotal EPCORE NHL-1 trial reaffirms subcutaneous epcoritamab induces deep, durable complete remissions in patients with relapsed/refractory large B-cell lymphoma. Poster presented at: European Hematology Association 2023 Congress; June 8-11, 2023; Frankfurt, Germany. Poster P1118.

3. Genmab showcases data from comprehensive epcoritamab development program in patients across B-cell lymphomas at European Hematology Association (EHA) Annual Meeting 2023. News release. Genmab. June 9, 2023. Accessed June 22, 2023. https://ir.genmab.com/news-releases/news-release-details/genmab-showcases-data-comprehensive-epcoritamab-development