A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma(waveLINE-004)

The primary objective of this study is to evaluate **zilovertamab vedotin** with respect to the objective response rate in patients with relapsed or refractory **Diffuse Large B Cell Lymphoma**. This assessment is conducted according to the Lugano Response Criteria and is evaluated by a Blinded Independent Central Review (BICR). The clinical relevance of this objective lies in its potential to provide insights into the efficacy of zilovertamab vedotin as a therapeutic option for patients who have not responded to prior treatments.

Secondary objectives include:

• Evaluating zilovertamab vedotin with respect to the duration of response per Lugano Response Criteria as assessed by BICR.
• Assessing the safety and tolerability of zilovertamab vedotin.

The clinical trial involves a total of **75 participants** diagnosed with **Diffuse Large B Cell Lymphoma**, a type of non-Hodgkin’s lymphoma, who have not responded to prior therapies. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including having relapsed or refractory diffuse large B-cell lymphoma, progression after at least two lines of prior therapy, and either post-chimeric antigen receptor T cell therapy failure or ineligibility for such therapy. All participants have a histologically confirmed diagnosis of the disease and radiographically measurable lymphoma per the Lugano Response Criteria. They must have a life expectancy of at least three months and an Eastern Cooperative Oncology Group performance status of 0 to 2. The trial also considers vulnerable populations, ensuring that all participants have adequate organ function. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **zilovertamab vedotin** in participants with relapsed or refractory **Diffuse Large B Cell Lymphoma** (DLBCL). This is a Phase 2, open-label study, where both participants and healthcare providers are aware of the treatment being administered. The primary objective is to assess the objective response rate according to the Lugano Response Criteria, as evaluated by a Blinded Independent Central Review (BICR). Secondary endpoints include the duration of response, the number of participants experiencing adverse events, and the number of participants discontinuing treatment due to adverse events.

The trial is expected to run from February 23, 2022, to February 10, 2026. Participants will be involved for a maximum treatment period of 96 weeks. The study involves the administration of zilovertamab vedotin via intravenous infusion, with a maximum daily dose of 2.5 mg/kg. The trial includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor response and safety, and an end-of-study visit to assess final outcomes. Participants must have a histologically confirmed diagnosis of DLBCL, have progressed after at least two lines of prior therapy, and meet other inclusion criteria such as adequate organ function and a life expectancy of at least three months.

Participants may be terminated early from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it in their best interest. The trial is not categorized as low intervention and is focused on evaluating the safety, efficacy, and dosing regimen of the investigational product in the target population. The study is sponsored by Merck & Co., Inc., and the investigational product is not a pediatric formulation nor classified as an orphan drug.

The clinical trial involves the administration of **Zilovertamab vedotin**, an investigational medication, to evaluate its efficacy and safety in participants with relapsed or refractory diffuse large B-cell lymphoma. **Zilovertamab vedotin** is provided in two pharmaceutical forms: a **solution for injection** and a **solution for infusion**. Both forms are administered via **intravenous infusion**. The dosage is calculated based on body weight, with a maximum daily dose of 2.5 mg/kg. The treatment period extends up to 96 weeks. The active substance, **Zilovertamab vedotin**, is a protein-based compound developed by Merck & Co. Inc., and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of **Zilovertamab vedotin**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the objective response rate according to the Lugano Response Criteria, as evaluated by a Blinded Independent Central Review.

The efficacy of **Zilovertamab vedotin** in the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**, as determined by the Lugano Response Criteria. This evaluation will be conducted by a Blinded Independent Central Review (BICR) to ensure objectivity and consistency in the assessment of responses in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The ORR serves as the primary endpoint of the study.

Secondary endpoints include the **Duration of Response (DOR)**, also evaluated per the Lugano Response Criteria, and the number of participants who experience an adverse event (AE) or discontinue study treatment due to an AE. These secondary endpoints will provide additional insights into the treatment's efficacy and safety profile. The trial is designed as a Phase 2 open-label study, focusing on both efficacy and safety, with a planned duration extending until February 2026.