NEW YORK (Reuters Health) – Single-agent subcutaneous epcoritamab appears to benefit patients with relapsed or refractory B-cell non-Hodgkin lymphoma, results of an ongoing early trial suggest.
Epcoritamab is “a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells,” the study team explains in The Lancet.
“Epcoritamab showed potent, single-agent, antitumor activity and an overall manageable safety profile,” report Dr. Martin Hutchings of Rigshospitalet in Copenhagen, Denmark, and colleagues. “Coupled with the mechanism of action and ease of administration of epcoritamab, these findings are highly encouraging for patients with relapsed or refractory B-cell non-Hodgkin lymphoma.”
They conducted a phase-1/2 study to establish the safety and best dose of epcoritamab. Over about two years, the research team enrolled 73 adults with relapsed or refractory CD20+ mature B-cell non-Hodgkin lymphoma at ten sites in Denmark, the Netherlands, the U.K. and Spain.
Eligible patients received priming and intermediate subcutaneous doses of epcoritamab, followed by full doses, in 28-day cycles. Each subsequent cohort involved escalating the priming, intermediate, or full dose (0.0128 to 60 mg).
The response rate was 68%, with 45% responding completely at full doses of 12 to 60 mg. At 48 mg, the response rate was 88%, with 38% responding completely. Overall, 90% of patients with relapsed or refractory follicular lymphoma responded, with 50% achieving complete response at full doses of 0.76 to 48 mg.
Epcoritamab induced robust and long-lasting B-cell depletion as well as CD4+ and CD8+ T-cell activation and expansion, with small increases in cytokine levels.
Common adverse events included pyrexia, cytokine release syndrome and injection-site reactions. There were no grade-3-or-higher cytokine-release-syndrome events, and no treatments were discontinued due to treatment-related adverse events or treatment-related deaths.
Two experts who were not involved in the study told Reuters Health that they welcome its results.
“Oncologists have long asked for a way to bring the immune system’s T lymphocytes within striking distance of cancer cells,” said Dr. Felipe Samaniego, a professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston. “Epcoritamab, an antibody that binds to both T-cells and B-cells, has brought that idea into reality.”
“These results are comparable to best results obtained with standard CAR-T (chimeric antigen receptor T-cell) cells, but requiring only a fraction of technology used in preparation of CAR-T cells,” Dr. Samaniego explained by email.
Dr. Alexey Danilov, a professor in the Division of Lymphoma at City of Hope Comprehensive Cancer Center in Duarte, California, said by email, “The study cites highly promising efficacy data using subcutaneous bi-specific antibody in patients with non-Hodgkin lymphoma.”
“While efficacy and durability of response will need to be confirmed in a larger cohort of patients, epcoritamab is a highly promising novel approach for this difficult-to-treat patient population,” he noted.
In a linked editorial, Drs. Armin Ghobadi and Nancy L. Bartlett of Washington University School of Medicine in St. Louis, Missouri, write, “On the basis of both the excellent efficacy and tolerability, epcoritamab and other bispecific redirectors are being explored in earlier lines of therapy, often in combination with other agents. Bispecific T-cell redirectors are anticipated to play an important role in improving outcomes for patients with B-cell non-Hodgkin lymphoma, especially if longer follow-up confirms durable remissions.”
Genmab and AbbVie funded the study.
Dr. Hutchings did not respond to requests for comment.
SOURCES: https://bit.ly/3tVpxxU and https://bit.ly/3nUfXdQ The Lancet, online September 8, 2021.
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