Merck's investigational antibody-drug conjugate (ADC), zilovertamab vedotin, has demonstrated promising results in a Phase 2 trial (waveLINE-007) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL). The trial, evaluating zilovertamab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP), achieved a 100% complete response rate (CR) in patients treated with a 1.75 mg/kg dose. These findings, presented at the 66th American Society of Hematology (ASH) Annual Meeting, have led to the selection of this dose for the ongoing Phase 3 trial.
Phase 2 waveLINE-007 Trial Results
The waveLINE-007 trial was a non-randomized, open-label Phase 2 study designed to assess the safety and efficacy of zilovertamab vedotin in combination with R-CHP in previously untreated DLBCL patients. A total of 36 patients were enrolled and received zilovertamab vedotin plus R-CHP intravenously every 21 days for up to eight cycles. The study included three treatment arms with varying doses of zilovertamab vedotin: 1.75 mg/kg (n=15), 2.0 mg/kg (n=15), and 2.25 mg/kg (n=6).
The efficacy results showed that a CR was achieved in 100% of patients receiving the 1.75 mg/kg dose (95% CI: 78.2-100.0), 93.3% of patients receiving the 2.0 mg/kg dose (95% CI: 68.1-99.8), and 100% of patients receiving the 2.25 mg/kg dose (95% CI: 54.1-100.0). The total CR rate at the end of treatment was 97.2% (95% CI: 85.5-99.9). The median follow-up for all patients was 17.6 months (range, 7.1-24.6). The objective response rate (ORR) was 100% for patients receiving the 1.75 mg/kg dose, 93.3% for patients receiving the 2.0 mg/kg dose, and 100% for patients receiving the 2.25 mg/kg dose, all in combination with R-CHP. The median duration of response (DOR) has not been reached for all patients, and the total 12-month DOR was 93.5%.
Serious treatment-related adverse events (TRAEs) occurred in 11% (n=4) of all patients. Grade 3-4 TRAEs occurred in 58% (n=21) of all patients. The most common of these events were neutropenia, nausea, anemia, and diarrhea.
Phase 3 waveLINE-010 Trial
Building on these encouraging Phase 2 results, Merck has initiated the pivotal Phase 3 waveLINE-010 trial (NCT06717347) to further evaluate zilovertamab vedotin in combination with R-CHP for patients with previously untreated DLBCL. This randomized, open-label trial will compare the zilovertamab vedotin plus R-CHP regimen to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) alone, the current standard of care.
The waveLINE-010 trial aims to enroll approximately 1,046 patients globally. The primary endpoint is progression-free survival (PFS), and secondary endpoints include complete response (CR) rate at the end of the treatment, overall survival, event-free survival, duration of CR, and safety.
About Zilovertamab Vedotin
Zilovertamab vedotin is an investigational ADC that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1), a transmembrane protein overexpressed in various hematologic malignancies. By targeting ROR1, zilovertamab vedotin aims to deliver a cytotoxic payload directly to cancer cells, minimizing damage to healthy cells.
DLBCL Landscape
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for approximately 25-30% of all NHL cases worldwide. In the U.S., an estimated 25,000 patients are diagnosed with DLBCL each year. While the five-year relative survival rate for DLBCL is 60-70%, there remains a need for additional first-line treatment options, as approximately 40% of patients still experience relapsed or refractory disease after initial treatment with the current standard of care.
Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories, stated, "Following the encouraging results observed in the Phase 2 waveLINE-007 trial, we look forward to evaluating the potential clinical benefits of a combination regimen with zilovertamab vedotin in patients with diffuse large B-cell lymphoma compared to the current standard treatment."
