Phase 3 Study of Epcoritamab for Advanced DLBCL to Open in Europe, Australia

Phase 3 Study of Epcoritamab for Advanced DLBCL to Open in Europe, Australia

Genmab is launching a Phase 3 clinical trial investigating its bispecific antibody epcoritamab as a treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients who fail to respond to, or are ineligible for, autologous stem cell transplant (ASCT).

The open-label trial (NCT04628494) is expected to enroll up to 480 people whose tumors are positive for the CD20 protein, and whose prior treatments included at least one chemotherapy regimen containing an anti-CD20 antibody. Patients can enroll at sites in Europe and Australia; information is available here.

“We look forward to the data from this first Phase 3 trial, especially for relapsed or refractory DLBCL patients as it remains an area of high unmet medical need,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.

Epcortimab is an antibody that specifically binds two proteins: CD20, found at the surface of some cancerous B-cells, and CD3, a protein produced by cytotoxic T-cells, a type of immune cell. The binding of the antibody to these two proteins brings the cancer and immune cells together, with an aim of improving immune responses.

The investigational medicine, which is delivered via a subcutaneous (under-the-skin) injection, is being co-developed by Genmab and AbbVie as part of a broad oncology collaboration.

The medication has been showing a favorable safety profile and signs of efficacy among DLBCL patients included in a Phase 1/2 trial (NCT03625037).

This study is investigating epcortimab among people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Most of the patients enrolled as of January — 73% — had DLBCL or high grade B-cell lymphoma (HGBCL), and had undergone a median of three prior lines of therapy.

Participants were given the antibody as a single injection in 28-day cycles, until their disease progressed or signs of unacceptable toxicity were reported. Epcortimab was given once a week for the first two cycles, every two weeks for cycles three through six, and once a month thereafter.

No dose-limiting toxicities had been reported, and the maximum tolerated dose was not reached. Most common side effects related to treatment were fever (71%), fatigue (46%), and injection site reaction (39%).  

A majority of patients (59%) experienced cytokine release syndromea severe immune reaction caused by the rapid and strong release of substances produced by activated immune cells. But these were all mild to moderate in nature, trial researchers reported, and all were resolved. 

Nine DLBCL/HGBCL patients, given epcortimab at doses of 6 mg or higher, were evaluated for efficacy. Five (56%) experienced a meaningful reduction in tumor burden, including four (44%) with a total disappearance of cancer. An additional two patients (22%) showed disease stabilization, amounting to a clinical benefit of 78%.

The upcoming Phase 3 trial is designed to confirm epcortimab’s benefits in this group of lymphoma patients. It will compare the safety and efficacy of this antibody to investigator choice of chemotherapy — R-GemOx (rituximab, bendamustine and oxaliplatin) or BR (bendamustine and rituximab).

The trial’s primary goal is to determine whether epcortimab extends patients’ overall survival. Secondary measures include the time patients live without disease worsening, response rates, duration of responses, time to response, and time to initiation of a new lymphoma treatment.

This Phase 3 trial is part of a broad clinical development plan for epcortimab. Genmab and AbbVie are also launching an open-label Phase 1/2 trial (NCT04623541) to test this antibody in patients with relapse or refractory chronic lymphocytic leukemia who received two or more prior lines of therapy.

“In collaboration with AbbVie, we have planned a broad, expansive, accelerated epcoritamab clinical development plan to maximize the potential of this promising bispecific antibody, with the ultimate goal of bringing new differentiated treatment options as soon as possible to patients,” van de Winkel said.