Phase 3 waveLINE-010 Study Starts for Zilovertamab Vedotin in DLBCL

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The phase 3 waveLINE-010 trial (NCT06717347) evaluating the combination of zilovertamab vedotin, an investigational antibody-drug conjugate (ADC), with rituximab (Rituxan) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) alone for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL), has been initiated.¹

WaveLINE-010 is a pivotal, randomized, open-label study which plans to enroll approximately 1046 patients globally. Global recruitment has begun, with patients now enrolling.

“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, oncology clinical research, Merck Research Laboratories, in a press release.

In the experimental arm of the study, patients will receive a dose of zilovertamab vedotin at 1.75 mg/kg plus 750 mg/m² cyclophosphamide, 50 mg/m² doxorubicin, and 375 mg/m² rituximab or rituximab biosimilar via intravenous (IV) infusion on day 1 of each 21-day cycle for up to 6 cycles.² Patients will also be given 100 mg prednisone or prednisolone via oral tablet per day during days 1 through 5 of each 21-day cycle for up to 6 cycles.

Those in the active comparator arm will be given cyclophosphamide at a dose of 750 mg/m² with 50 via IV infusion on day 1 of each 21-day cycle for up to 6 cycles. Patients in this arm also will be given prednisone at a 100 mg dose or prednisolone via oral tablet per day during days 1-5 of each 21-day cycle for up to 6 cycles.

Enrollment is open to patients who have a histologically confirmed diagnosis of DLBCL by prior biopsy, based on local testing according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues. Patients are required to have received no prior treatment for their DLBCL and have PET-positive disease at the time of screening, defined as 4 to 5 on the Lugano 5-point scale. Further, patients must have an ECOG performance status of 0, 1, or 2 and an ejection fraction ≥45% as determined by either echocardiogram or multigated acquisition.

Patients with human immunodeficiency virus (HIV) must have well controlled HIV on antiretroviral therapy. Those who are hepatitis B surface antigen-positive are eligible for enrollment if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load prior to randomization. Additionally, patients with a history of hepatitis C virus (HCV) infection may be included if HCV viral load is undetectable at screening.

The primary end point of the study is progression-free survival. Secondary end points include complete response (CR) rate at the end of the treatment, overall survival, duration of CR, event-free survival, and safety.

In addition to this study, zilovertamab vedotin is being assessed in the phase 2/3 waveLINE-003 dose confirmation and expansion trial (NCT05139017) for treating patients with relapsed/refractory DLBCL, as well as in the phase 2 waveLINE-007 trial (NCT05406401) where the agent is being given to patients with previously untreated DLBCL in combination with R-CHP.¹

“ADCs have shown promise as an important modality in the treatment of different cancer types, and the initiation of this phase 3 waveLINE clinical trial demonstrates our commitment to researching zilovertamab vedotin to help address unmet needs for patients with this aggressive and most common form of non-Hodgkin lymphoma,” added Lubiniecki in the press release.

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. News release. Merck. February 6, 2025. Accessed February 6, 2025. https://tinyurl.com/2j4wnmjw

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). ClinicalTrials.gov. Updated January 30, 2025. Accessed February 6, 2025. https://clinicaltrials.gov/study/NCT06717347