At a median follow-up of 10.7 months, the overall response rate was 63.1%.
The subcutaneous CD3xCD20 bispecific T-cell–engaging antibody epcoritamab (Epkinly) leads to deep and durable responses in highly refractory patients with large B-cell lymphoma (LBCL), according to a new report.
The authors found the therapy had a manageable safety profile, and also worked on patients with previous exposure to chimeric antigen receptor (CAR) T-cell therapy. The study was published in the Journal of Clinical Oncology.
Corresponding author Catherine Thieblemont, MD, PhD, of the University of Paris, and colleagues, said despite the development of new therapies for LBCL, managing relapsed or refractory cases is a challenge.
“Outcomes are poor, particularly among patients with early relapse or primary refractory disease,” they wrote.
A previous study of patients who relapsed or were refractory to first-line chemoimmunotherapy had a median overall survival of just 6.3 months, they noted. The authors said CAR T-cell therapy is one of the most exciting advancements in LBCL therapy, but noted that access to the treatment remains limited.
“Thus, an unmet medical need still remains for effective, well-tolerated, and convenient therapies,” they said.
The subcutaneously administered epcoritamab targets both CD3 and CD20 and redirects and activates T cells to kill malignant cells that express CD20, Thieblemont and colleagues said.
A previous dose-escalation portion of the study established a recommended phase II dose and there was no dose-limiting toxicity in patients with relapsed or refractory CD20-positive mature B-cell non-Hodgkin lymphoma. The new study results are from an LBCL expansion cohort. The study was a single-arm, multicenter, open-label study.
The study protocol called for patients with LBCL who had previously undergone two lines of therapy to receive subcutaneous epcoritamab in 28-day cycles. In the first cycle, patients received weekly step-up doses for the first 3 weeks. They then received full weekly doses through cycle 3, followed by doses every 2 weeks in cycles 4-9 and once every 4 weeks from cycle 10 onward until disease progression or unacceptable toxicity.
A total of 157 patients were treated, and those patients had had a median of 3 prior lines of therapy. The majority of patients (61.1%) had primary refractory disease, and 38.9% had prior exposure to CAR T-cells.
After a median follow-up of 10.7 months, 63.1% of patients had shown a response (95% confidence interval [CI] 55.0-70.6). The complete response rate was 38.9% (95% CI, 31.2-46.9).
“Responses were primarily observed early, by either the first or the second response assessment (scheduled at weeks 6 and 12),” Thieblemont and colleagues wrote.
The median duration of response was 12.0 months, and the median progression-free survival (PFS) was 4.4 months. Among complete-responders, neither the median duration of response nor the median PFS was reached. The median overall survival was also not reached, the authors said.
In terms of safety, 12 patients discontinued therapy due to treatment-emergent adverse events, and 3 patients stopped participating due to treatment-related adverse events. About half (49.7%) of patients experienced cytokine release syndrome, though almost all cases were grade 1 or 2. Pyrexia (23.6%) and fatigue (22.9%) were the other most-common treatment-emergent adverse events. Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients. Nine patients had fatal treatment-emergent adverse events.
The authors said the safety profile they found was consistent with previous reports, and they said the majority of adverse events occurred within the first 12 weeks of the treatment.
“These results support ongoing and future clinical trials of epcoritamab both as monotherapy and in combination in late and earlier lines of treatment for B-cell non-Hodgkin lymphoma,” they concluded.
Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023;41(12):2238-2247. doi:10.1200/JCO.22.01725