Subcutaneous epcoritamab, a bispecific antibody, has demonstrated deep and durable responses in a large expansion cohort of patients with relapsed or refractory large B-cell lymphoma (LBCL), according to late-breaking data presented during the European Hematology Association (EHA) 2022 Congress in Vienna.1 Epcoritamab simultaneously binds to CD3 on T cells and CD20 on B cells.
Primary results of the phase II EPCORE™ NHL-1 trial showed an overall response rate of 63% and a complete response rate of 39% in patients who had previously received at least two lines of systemic antilymphoma therapy. Efficacy with deep and durable responses was also seen in 54% who had previously been treated with chimeric antigen receptor (CAR) T-cell therapy, including a 34% complete response rate, with the bispecific antibody.
“Some treatment approaches for large B-cell lymphoma, such as 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,” said Catherine Thieblemont, MD, PhD, Head of the Hemato-Oncology Department at Hôpital Saint-Louis, Paris. “The data presented here suggest that epcoritamab has the potential to provide patients living with relapsed or refractory large B-cell lymphoma an accessible, effective treatment, with a safety profile that may fulfill an unmet need.”
Catherine Thieblemont, MD, PhD
As Dr. Thieblemont explained, large B-cell lymphoma is a fast-growing, difficult-to-treat type of aggressive non-Hodgkin lymphoma. There are an estimated 150,000 new cases each year globally.
“Despite therapeutic advancements made in recent years, [relapsed/refractory] large B-cell lymphoma remains a difficult disease, and most patients have a poor prognosis,” she explained. “There is a need for convenient, efficacious, well-tolerated, and readily available treatment options.”
Study Methods
In the EPCORE NHL-1 dose-escalation cohort across histologies, subcutaneous epcoritamab demonstrated single-agent activity with clinically meaningful overall and complete response rates along with a manageable safety profile.2 During the EHA 2022 Congress, Dr. Thieblemont and colleagues presented dose-expansion results in patients with relapsed or refractory CD20-positive large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
Patients received epcoritamab (priming and intermediate doses followed by full doses of 48 mg) as 1-mL subcutaneous injections every 28 days until disease progression or unacceptable toxicity. Mitigation of cytokine-release syndrome included step-up dosing and corticosteroid prophylaxis in the first cycle alone. Per protocol, 24-hour hospitalization was required only for the first full dose to ensure close observation of patients.
The study’s primary endpoint was overall response rate by independent review committee. Key secondary endpoints included the duration of response, time to response, progression-free survival, overall survival, complete response rate, safety, and tolerability.
Responses in Highly Refractory Disease
The study cohort included 157 patients with relapsed or refractory large B-cell lymphoma who were previously treated with a median of three lines of therapy. According to baseline characteristics, 61% of patients were refractory to primary treatment, 20% had prior autologous stem cell transplantation, and 39% were treated with CAR T-cell therapy (75% of whom were refractory to CAR T-cell therapy).
With a median follow-up of 10.7 months, findings for the total patient population showed an overall response rate of 63% and a complete response rate of 39%. Patients who were naive to CAR T-cell therapy achieved a 69% overall response rate and a 42% complete response rate, whereas those who received prior CAR T-cell treatment achieved a 54% overall response rate and a 34% complete response rate.
The median duration of response was approximately 12 months. The median duration of response among patients achieving a complete response has not been reached, however, with 89% still in complete response at 9 months.
Safety Profile
The safety profile of epcoritamab was manageable and consistent with previous findings, said Dr. Thieblemont, with most treatment-emergent adverse events resolving during the first 12 weeks of treatment. The most common treatment-emergent adverse events of any grade (≥ 15%) included cytokine-release syndrome (49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), diarrhea (20.4%), injection-site reaction (19.7%), nausea (19.7%), and anemia (17.8%).
The most common grade 3 or 4 treatment-emergent adverse events (≥ 5%) included neutropenia (14.6%), anemia (10.2%), neutrophil count decrease (6.4%), and thrombocytopenia (5.7%). The observed grade 3 cytokine-release syndrome was low (2.5%). No grade 4 or 5 cytokine-release syndrome was observed.
There is an ongoing phase III, open-label, randomized trial evaluating epcoritamab as monotherapy in patients with relapsed or refractory DLBCL. Investigators are also exploring epcoritamab in combination across lines of therapy for a variety of hematologic malignancies.
DISCLOSURE: Dr. Thieblemont reported financial relationships with Bristol Myers Squibb/Celgene, Hospira, Roche, AbbVie, Amgen, Cellectis, Bayer, Gilead Sciences, Incyte, Janssen, Kite, Novartis, and Takeda.
REFERENCES
1. 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. EHA 2022 Congress. Abstract LB2364. Presented June 11, 2022.
2. Hutchings M, Mous R, Clausen MR, et al: Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: An open-label, phase 1/2 study. Lancet 398:1157-1169, 2021.
