Merck Launches Phase III Trial Evaluating Zilovertamab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

Image Credit: Adobe Stock Images/LASZLO

Merck has initiated the pivotal Phase III waveLINE trial to evaluate zilovertamab vedotin, an investigational antibody-drug conjugate (ADC), in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL). According to the company, the trial will compare this regimen against the current standard of care, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).¹

“Following the encouraging results observed in the Phase II 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, VP, oncology clinical research, Merck Research Laboratories, in a press release. “ADCs have shown promise as an important modality in the treatment of different cancer types, and the initiation of this Phase III 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.”

The randomized, open-label WaveLINE-010 trial seeks to enroll 1,046 patients globally. The primary endpoint of the trial is progression-free survival, with secondary endpoints including complete response (CR) rate at the end of the treatment, overall survival, event-free survival, duration of CR and safety.

According to the MD Anderson Cancer Center, DLBCL is the most common form of B-cell lymphoma. It mostly affects older people, with an average onset age of 60 years. Data suggest that overall cure rates in the past 15 years have been around 70%.² According to the Lymphoma Research Foundation, DLBCL accounts for 22% of newly diagnosed cases of B-cell non-Hodgkin lymphomas (NHL) in the United States, with over 18,000 people receiving a diagnosis each year.³

According to the American Cancer Society, NHL is one of the most common cancers in the United States, accounting for 4% of all cases. It is expected that by the end of the year, 80,350 people will be diagnosed with it and an estimated 19,390 people will die as a result. In most cases, it is more common in men, who maintain a one in 44 chance, while women have a one in 54 chance of developing it during their lifetime. NHL can occur at any age, with data showing that it is one of the most common cancers in children, teenagers, and young adults. However, chances increase with age, as more than half of patients are first diagnosed over 65 years of age.⁴

According to the National Cancer Institute, NHL accounted for approximately 4% of all new cancer cases in the United States in 2024 and caused approximately 3.3% of all cancer-related deaths. Data also found that in 2021, there were an estimated 808,413 people living with NHL in the United States. Additionally, the rate of new cases of NHL was 18.6 per 100,000 men and women per year; however, death rates fell 2.1% between 2013 and 2022.⁵

Currently, zilovertamab vedotin is being evaluated for the treatment of relapsed or refractory DLBCL as well as in combination with R-CHP in patients with previously untreated DLBCL in the Phase II/III waveLINE-003 dose confirmation and expansion trial and the Phase II waveLINE-007 trial, respectively. Data were first presented in December 2024 at the 66^th American Society of Hematology Annual Meeting and Exposition.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. February 6, 2025. Accessed February 6, 2025. https://www.merck.com/news/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/

2. B-cell Lymphoma. MD Anderson. Accessed February 6, 2025. https://www.mdanderson.org/cancer-types/non-hodgkin-lymphoma/b-cell-lymphoma.html#:~:text=B%2Dcell%20lymphoma%20is%20a,United%20States%20are%20B%2Dcell.

3. What is Lymphoma? Lymphoma Research Foundation. Accessed February 6, 2025. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/dlbcl/#:~:text=Diffuse%20large%20B%2Dcell%20lymphoma%20(DLBCL)%20is%20the%20most,age%20of%2060%20at%20diagnosis.

4. Key Statistics for Non-Hodgkin Lymphoma. American Cancer Society. Accessed February 6, 2025. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html

5. Cancer Stat Facts: Non-Hodgkin Lymphoma. NIH. Accessed February 6, 2025. https://seer.cancer.gov/statfacts/html/nhl.html