A clinical trial comparing two combination therapies for diffuse large B-cell lymphoma (DLBCL): Zilovertamab vedotin versus polatuzumab vedotin combined with the standard R-CHPt regimen (MK-2140-011/waveLINE-011)

Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma (lymph node cancer) in adults. It arises from B lymphocytes, a subgroup of white blood cells—the cells normally responsible for the body’s immune defense. Based on certain biological characteristics, DLBCL is classified into various subgroups, including the so-called germinal center B-cell subtype (GCB). This classification can be important for choosing a treatment strategy. The standard treatment for newly diagnosed DLBCL consists of a combination of immunotherapy and chemotherapy. A commonly used regimen is R-CHP, consisting of rituximab, cyclophosphamide, doxorubicin, and prednisone.

In standard treatment, the R-CHP regimen is combined with the drug polatuzumab vedotin (Pola-R-CHP). Polatuzumab vedotin is what is known as an antibody-drug conjugate: an antibody specifically binds to the cancer cells and delivers a cytotoxic agent directly into the cell to destroy it. This study aims to investigate another antibody-drug conjugate, zilovertamab vedotin, in combination with R-CHP. The drug has not yet been approved for the treatment of DLBCL.

The goal of this Phase 2 study is to determine whether treatment with zilovertamab vedotin is more effective at completely eliminating the cancer (complete response) than treatment with polatuzumab vedotin. Additional objectives include comparing overall survival and tolerability. Patients will be randomly assigned to two groups. The study is open-label (not blinded), meaning that both medical staff and patients know which treatment is being administered. Group A receives zilovertamab vedotin in combination with R-CHP. Group B receives polatuzumab vedotin in combination with R-CHP. Both combinations are administered as an intravenous infusion every three weeks for a total of six treatment cycles (approximately four months). Patients with an increased risk of relapse will also receive two additional cycles of rituximab. The success of the treatment is regularly monitored through tests (e.g., PET-CT scans).

Adults aged 18 and older with newly diagnosed, untreated DLBCL of the GCB subtype are eligible to participate. The disease must be confirmed by a tissue sample and detectable on an imaging test (PET-CT scan). In addition, patients must be healthy enough to undergo the therapy (e.g., good heart, liver, and kidney function).