Promising Efficacy Results Demonstrated With Epcoritamab in Refractory LBCL

Clinically meaningful efficacy seen with epcoritamab in patients with highly refractory large B-cell lymphoma, according to data from the phase 2 EPCORE NHL-1 clinical trial.

Epcoritamab (GEN3013; DuoBody-CD3xCD20) demonstrated clinically meaningful efficacy in challenging to treat patients with highly refractory large B-cell lymphoma (LBCL), including those who were previously treated with chimeric antigen receptor (CAR) T-cell therapy, according to Genmab.1

Data from the expansion cohort of the phase 2 EPCORE NHL-1 clinical trial (NCT04663347) evaluating the safety and efficacy of subcutaneous epcoritamab in this patient population were presented at the 2022 European Hematology Association Annual Meeting.2

Findings revealed that patients who previously had received 2 or more prior lines of systemic anti-lymphoma therapy treated with epcoritamab demonstrated deep and durable responses, including an overall response rate (ORR) of 63% and a complete response (CR) rate of 39%. Additionally, CAR T-cell therapy treatment-naïve patients achieved an ORR of 69% and a CR rate of 42%. Patients who were previously treated with CAR T cells showed an ORR of 54% and a CR rate of 34%.

“Large B-cell lymphoma is a fast-growing, difficult to treat type of aggressive non-Hodgkin’s lymphoma. Some treatment approaches like chemotherapy and immunotherapy have been in place for decades and newer treatments like CAR T-cell therapies involve multiple steps before a patient can begin treatment, so there is still a need for additional treatment options,” stated Catherine Thieblemont, MD, PhD, head of the Hemato-Oncology Department at Hôpital Saint-Louis, Paris, France, in the press release. “The data presented today suggest that epcoritamab has the potential to provide patients living with relapsed/refractory LBCL and accessible, effective treatment with a safety profile that may fulfill an unmet need.”

Epcoritamab is a bispecific antibody that binds to CD3 on T cells and CD20 on B cells and is administered subcutaneously. In the ongoing, open-label, multinational, interventional phase 1/2b EPCORE NHL-1 trial, the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with standard-of-care (SOC) agents are being examined in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin lymphoma (NHL), including LBCL and diffuse LBCL.

Phase 1 of the trial consists of a first-in-human, dose-escalation portion, and phase 2 is the expansion and optimization part. This study cohort includes 157 patients with relapsed/refractory LBCL who were previously treated with a median of 3 lines of prior therapy.3 Enrollment in this cohort consisted of patients who were refractory to primary treatment (61%), those who had prior autologous stem cell transplantation (ASCT; 20%), and patients who were treated with CAR T-cell therapy (29%).

The primary end point of the phase 2 expansion portion of the trial was ORR as assessed by an independent review committee, with secondary efficacy end points including duration of response (DOR), CR rate, progression-free survival, and time to response, as determined by the Lugano criteria. Other outcome measures evaluated in the trial included time to next therapy and the rate of minimal residual disease negativity.

The median DOR after a median follow-up of 10.7 months was estimated to be 12 months, and the median DOR for patients achieving a CR was not reached, with a total of 89% of patients remaining in CR at 9 months.

In regard to safety, epcoritamab demonstrated a manageable safety profile that was consistent with previous findings. Most of the treatment-emergent AEs (TEAEs) occurred during the first 12 weeks of treatment and quickly resolved. Cytokine release syndrome (CRS) was the most common TEAE of any grade (in greater than or equal to 15% of patients), which occurred in 49.7% of patients, followed by pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), diarrhea (20.4%), injection site reaction (19.7%), nausea (19.7%), and anemia (17.8%).

Additionally, the most common grade 3 or 4 TEAEs seen in patients consisted of neutropenia (14.6%), anemia (10.2%), neutrophil count decrease (6.4%), and thrombocytopenia (5.7%). The observed grade 3 CRS rate was 2.5%, and no grade 4/5 CRS events were observed throughout the trial. Treatment was tocilizumab (Actemra) was required for 14% of patients. Additionally, 6.4% of patients experienced an immune effector cell-associated neurotoxicity syndrome (ICANS) event; all but 1 of these cases was grade 1 or 2, and a case of grade 5 ICANS was the only treatment-related death. Few AE-related treatment discontinuations were required.

“These latest data are promising because they suggest that treatment with epcoritamab may benefit patients with this fast-growing, aggressive and difficult to treat type of non-Hodgkin’s lymphoma who are in need of new therapeutic advances,” added Jan van de Winkel, PhD, chief executive officer of Genmab, in the press release. “We are encouraged by the potential of epcoritamab and look forward to continuing to advance our robust clinical development program with our partner, AbbVie.”

References:
1. Genmab announces late-breaking phase 2 trial results of investigational epcoritamab (DuoBody®-CD3xCD20) in relapsed/refractory large B-cell lymphoma (LBCL) patients presented at european hematology association (EHA) presidential symposium. News release. Genmab. June 11, 2022. Accessed June 13, 2022. https://bit.ly/3aUaRJP
2. 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 Annual Meeting; June 9-17, 2022; Vienna, Austria. Abstract LB2364. https://bit.ly/3xq326p
3. Genmab and abbVie announce topline results for epcoritamab (DuoBody®-CD3xCD20) from phase 1/2 trial in patients with relapsed/refractory large B-cell lymphoma (LBCL). News release. Genmab. April 13, 2022. Accessed June 13, 2022. https://bit.ly/3tA8gvn