Study on Two New Drugs for Certain Aggressive Lymphomas Following Relapse or Treatment Failure

Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) are among the aggressive forms of non-Hodgkin lymphoma. They grow rapidly, spread quickly throughout the body, and do not always respond permanently to existing treatments. Grade 3B follicular lymphoma (FL) also behaves like an aggressive lymphoma. Over time, the disease may recur or become unresponsive to treatment (refractory). In advanced stages of the disease or following relapses, standard therapies such as chemotherapy or antibody therapies are often no longer sufficient. Combination therapy using two modern antibody therapies—loncastuximab tesirin and epcoritamab—could represent a new treatment option in this context. The two active ingredients used have different, complementary mechanisms of action. Loncastuximab-tesirin is what is known as an antibody-drug conjugate. It specifically binds to the CD19 protein on the surface of cancer cells and delivers a cell-damaging agent into the tumor cell, triggering its death. Epcoritamab is a bispecific antibody that simultaneously recognizes T cells of the immune system and CD20-positive cancer cells. This directs the body’s own immune cells specifically to the tumor cells and activates them.

Epcoritamab is already approved as a monotherapy for the treatment of relapsed or refractory DLBCL, HGBL, and Grade 3B FL. Loncastuximab-tesirin is approved for the treatment of relapsed or refractory DLBCL and HGBL. The combination of these two active ingredients is not currently approved.

The goal of this Phase 2 study is to investigate the efficacy and safety of the combination therapy of loncastuximab tesirin and epcoritamab. Treatment with the combination therapy as part of the study is administered in multiple cycles. The duration and dosage are determined by the study protocol and the instructions of the treating physicians. Loncastuximab-tesirin is administered as an infusion through a venous access site (intravenously), and epcoritamab is injected under the skin (subcutaneously). The study is open-label, meaning that both the medical staff and the patient know which treatment is being administered. As part of the treatment, regular physical examinations, blood tests, and imaging procedures are performed to monitor the therapy. After completion of therapy, regular follow-up examinations are scheduled to assess the long-term effectiveness of the treatment and the occurrence of any potential side effects. The primary endpoint of the study is the overall response rate (ORR) to therapy at up to twelve months—that is, the proportion of patients in whom a measurable reduction in tumor size is observed during treatment.

Women and men aged 18 and older with relapsed or refractory DLBCL, HGBL, or FL Grade 3B are eligible to participate in this study. Patients must have previously received either anti-CD20 antibody therapy (e.g., rituximab) as first-line treatment or CAR-T cell therapy as second-line treatment, to which the disease did not respond permanently.