Longer follow-up demonstrated the antitumor activity of subcutaneous epcoritamab, which induced durable, clinically meaningful responses among relapsed/refractory B-cell non-Hodgkin lymphoma patients. The findings, which were presented at the ASCO 2021 Annual Meeting, also confirmed the consistent safety profile of this approach (Abstract 7518).
Despite recent treatment advancements, relapsed/refractory B-cell non-Hodgkin lymphoma is associated with a poor prognosis and there remains a need for chemotherapy-free, efficacious agents with manageable safety profiles and off-the-shelf dosing, according to the researchers.
"Epcoritamab is a full-length IgG1 bispecific antibody consisting of a humanized mouse anti-human CD3 monoclonal antibody and a human anti-CD20 monoclonal antibody," said study author Michael Clausen, MD, PhD, who explained that epcoritamab harnesses the patient's immune system to induce T-cell-mediated killing of CD20-positive malignant B cells.
"In this ongoing, Phase I/II study of single-agent, subcutaneous epcoritamab, the recommended Phase II dose was determined to be 48 mg," he noted. "Doses up to 60 mg-the maximum tolerated dose-were not reached and no dose-limiting toxicities were observed. Patients received subcutaneous epcoritamab in 28-day cycles until disease progression or unacceptable toxicity."
To reduce the occurrence and severity of potential cytokine release syndrome (CRS), the researchers used a priming dose and an intermediate dose of epcoritamab prior to the full dose, and prophylactic treatment with corticosteroids and antihistamines. At ASCO, Clausen reported on updated data with a longer follow-up, including progression-free survival.
Safety Findings
As of January 31, 2021, 68 patients with R/R B-cell non-Hodgkin lymphoma were enrolled across various histologies. This included de novo and transformed diffuse large B-cell lymphoma (DLBCL; n=46), follicular lymphoma (FL; n=12), mantle cell lymphoma (MCL; n=4), and others (n=6).
The median age was 68 years, and the patient population was heavily pretreated with a median of three and five prior lines of treatment in patients with DLBCL and FL, respectively, according to Clausen. "Ten percent of patients had received prior autologous stem cell transplantation and 9 percent had received CAR T-cell therapy," he said.
At a median follow-up of 14.1 months, the researchers reported that treatment was ongoing in 15 patients. Most drug discontinuations were a result of progressive disease (n=46). No patients stopped treatment due to treatment-related adverse events.
Treatment-emergent adverse events were primarily Grade 1, and the most common were pyrexia (69%), CRS (59%), and injection site reaction (47%), according to the study authors. Adverse events of special interest occurred in approximately 62 percent of patients, Clausen noted.
"All CRS events were Grade 1 or 2," he reported during his presentation. "Neurotoxicity was limited, manageable, and transient, lasting a median of 1.4 days. One case of Grade 3 tumor lysis syndrome was observed in the setting of retroperitoneal hemorrhage related to disease progression in a patient with bulky disease. There were no cases of febrile neutropenia and no treatment-related deaths."
Clinical Activity
In terms of efficacy, the researchers observed objective responses across histologies, with a median time to response of 1.4 months. "Overall response rate was 68 percent," said Clausen. "In patients receiving 48 mg to 60 mg, the overall response rate was 91 percent, with approximately half of patients achieving a complete response."
The study showed that responses deepened over time among patients with R/R DLBCL, FL, and MCL. Clausen reported that patients with FL who were treated with doses of 12 mg or more had an overall response rate of 80 percent, with 60 percent achieving a complete response.
All four of the evaluable patients with R/R DLBCL-who had received prior CAR T-cell therapy-responded to epcoritamab treatment, according to the study authors. Sixteen of 19 patients with R/R DLBCL, FL, or MCL who achieved a complete response remained in remission at the time of the data cutoff. The median progression-free survival for patients with R/R DLBCL who received a dose of 12 mg or more was 9.1 months and was not reached for patients who received 48 mg or more.
"In summary, subcutaneous epcoritamab continues to demonstrate a manageable safety profile with no new findings as well as high, single-agent activity with deep and durable responses in heavily pre-treated patients with R/R B-cell non-Hodgkin lymphoma," Clausen reiterated, while also emphasizing the durable responses observed with this treatment.
The expansion part of this study is ongoing and based on the current results of this first-in-human trial, epcoritamab is currently being explored in several studies, including a Phase III trial as a single-agent versus investigator's choice of standard-of-care chemotherapy in patients with R/R DLBCL who are not candidates for high-dose therapy.
Catlin Nalley is a contributing writer.