WaveLINE-010 Trial to Evaluate Zilovertamab Vedotin in Untreated DLBCL

The randomized, open-label, phase III waveLINE-010 trial will evaluate zilovertamab vedotin in combination with R-CHP versus R-CHOP for the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL), according to a press release from Merck.¹ The trial is enrolling approximately 1,046 adult patients globally.

Zilovertamab vedotin, an investigational antibody-drug conjugate, targets the receptor tyrosine kinase–like orphan receptor 1, a protein overexpressed in several hematologic malignancies.¹ The drug will be administered intravenously at the recommended phase II dose of 1.75 mg/kg.²

The study’s primary endpoint is progression-free survival. Secondary endpoints include complete response (CR) at end of treatment, overall survival, event-free survival, duration of complete response (DOR), number of patients who experience an adverse event, number of patients who discontinue the study due to an adverse event, and change from baseline in health-related quality of life.²

Zilovertamab vedotin plus R-CHP demonstrated promising efficacy and safety in the phase II waveLINE-007 trial presented at the 66th American Society of Hematology Annual Meeting & Exposition. At the recommended phase II dose of 1.75 mg/kg, the combination achieved an objective response rate of 100%, a CR rate of 100%, and a 12-month DOR of 90%. Six of 15 (40%) patients experienced grade 3-4 adverse events, most commonly neutropenia. One patient had disease progression after 12 weeks of follow-up.³

“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,” said Gregory Lubiniecki, MD, vice president of oncology clinical research at Merck Research Laboratories, in the press release.¹

References

1. Merck announces phase 3 waveLINE-010 trial initiation evaluating zilovertamab vedotin, an investigational antibody-drug conjugate, for the treatment of patients with previously untreated diffuse large B-cell lymphoma. BusinessWire. February 6, 2025. Accessed February 10, 2025.
2. A study to evaluate zilovertamab vedotin (MK-2140) combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated DLBCL (MK-2140-010). Clinical Trials. Last updated January 30, 2025. Accessed February 10, 2025.
3. Ozcan M, Gonzalez Barca E, Kim TM, et al. Waveline-007: dose escalation and confirmation, and efficacy expansion trial of zilovertamab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone plus rituximab in patients with diffuse large B cell lymphoma. Abstract #578. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.