Epcoritamab Monotherapy Demonstrates Promising Early Findings for Patients With R/R B-Cell non-Hodgkin Lymphoma

Subcutaneous single agent epcoritamab yielded promising results warranting further examination in a population of patients with relapsed/refractory B-cell non-Hodgkin lymphoma, according to findings from a phase 1/2 study (NCT03625037) published in Lancet.¹

The overall response rate (ORR) among patients who received full doses of epcoritamab at a dose of 12 mg to 60 mg was 68% (95% CI, 45%-86%) including a complete response (CR) rate of 45%. Patients treated with a 48 mg dose achieved an ORR of 99% (95% CI, 47%-100%), including a CR rate of 38%. Additionally, a population of patients with relapsed/refractory follicular lymphoma who were treated with a 0.76 mg to 48 mg dose of epcoritamab experienced an ORR of 90% (95% CI, 55%-100%), including a CR rate of 50%.

“The publication of these data in The Lancet, coupled with the presentation of the results at multiple medical congresses, demonstrate the importance of these early results and underscore the significant interest in the potential of next generation antibody therapeutic options for patients diagnosed with hematologic malignancies, whose current treatments may not be providing benefit,” Jan van de Winkel, PhD, chief executive officer at Genmab, said in a press release.² “Together with our partner, AbbVie, we are committed to evaluating the safety and efficacy of epcoritamab in patients diagnosed with B-cell lymphomas and other hematologic malignancies.”

The first in-human, multicenter, open label trial enrolled patients 18 years old or older with relapsed, progressive, or refractory CD20-positive mature B-cell non-Hodgkin lymphoma. Investigators enrolled 73 patients in the dose escalation portion of the trial and 68 to receive full doses, including 24 mg or less (n = 53), 48 mg (n = 12), or 60 mg (n = 3). In the phase 1 portion of the study, predefined priming doses or intermediate doses of epcoritamab were administered over 2 weeks followed by full doses of the agent ranging from 0.128 mg to 60 mg. Dose escalation was conducted utilizing a 3+3 design.

The primary outcome of the dose escalation portion of the trial was to identify the maximum-tolerated dose and recommended phase 2 dose of epcoritamab. Other end points included antitumor activity and treatment response, progression-free survival, and pharmacokinetic parameters.

The majority of patients had diffuse large B-cell lymphoma (68%) with other patients having follicular lymphoma (18%), mantle cell lymphoma (6%), and high grade B-cell lymphoma (4%). Additionally, 3 patients had primary mediastinal large B-cell lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma.

A total of 22% of patients remained on treatment with epcoritamab as of the data cutoff on January 31, 2021. Patients most commonly discontinued treatment due to progressive disease (68%), with 1 patient discontinuing due to an unrelated fatal adverse effect (AE). Notably, no patients discontinued due to treatment-related AEs (TRAEs). No dose limiting toxicities were reported and the maximum-tolerated dose had not been reached.

The most common treatment-emergent AEs (TEAEs) included pyrexia (69%), primarily associated with cytokine release syndrome (59%), and injection site reactions (47%). Nearly all incidences of pyrexia were grade 1/2 (91%), and all but 1 injection site reaction were grade 1. The only serious TRAE was pyrexia, which occurred in 5% of patients. The most common grade 3 TEAEs included anemia (13%), pyrexia (6%), fatigue (6%), and hypotension (6%), with 1 reported case of grade 4 dyspnoea.

“These initial trial results are encouraging, and their publication in The Lancet speaks to the strong interest from the clinical community in this important area of study. We look forward to further study of epcoritamab in B-cell lymphomas and other hematologic malignancies, and our continued pursuit of potential new treatment options for patients,” Mohamed Zaki, MD, PhD, vice president and head of global oncology development at AbbVie, concluded.

References

1. 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. Online first, September 8, 2021.
2. Clinical trial of investigational epcoritamab (DuoBody®-CD3xCD20) in patients with relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL) published in The Lancet. News release. AbbVie. September 9, 2021. Accessed September 9, 2021. https://bit.ly/3hf2rgM