Zilovertamab Vedotin + Standard of Care for Diffuse Large B-Cell Lymphoma
Trial Summary
What is the purpose of this trial?
The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have ongoing corticosteroid therapy or have received certain treatments like systemic anticancer therapy or radiotherapy within 4 weeks before starting the study.
What data supports the effectiveness of the drug Zilovertamab Vedotin combined with standard care for Diffuse Large B-Cell Lymphoma?
The combination of bendamustine and rituximab, which are part of the standard care, has shown modest effectiveness in treating relapsed and refractory diffuse large B-cell lymphoma, with a 45.8% overall response rate. Additionally, polatuzumab vedotin, a similar drug to zilovertamab vedotin, combined with bendamustine and rituximab, has shown promising results in aggressive B-cell lymphomas, with a 43% response rate in a real-life study.12345
Is the combination of Zilovertamab Vedotin and standard treatments safe for diffuse large B-cell lymphoma?
The combination of polatuzumab vedotin with bendamustine and rituximab has been studied in patients with relapsed or refractory diffuse large B-cell lymphoma, showing a manageable safety profile with common side effects like low blood cell counts. Bendamustine and rituximab have been used safely in various blood cancers, with known side effects including low blood cell counts and manageable toxicities.56789
What makes the drug Zilovertamab Vedotin unique for treating diffuse large B-cell lymphoma?
Research Team
Medical Director
Principal Investigator
Merck Sharp & Dohme LLC
Eligibility Criteria
Adults with relapsed or refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) who have measurable disease, an ECOG status of 0 to 2, and adequate organ function. They must have failed previous therapies and be able to provide a tumor tissue sample. Exclusions include those with certain medical conditions, recent treatments or vaccinations, active infections like HIV or Hepatitis C, significant heart issues, CNS lymphoma involvement, ongoing corticosteroid therapy, and other specific health concerns.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Dose Confirmation (Part 1)
Participants receive ZV in combination with R-GemOx or BR to confirm the dose
Efficacy Expansion (Part 2)
Participants receive the recommended Phase 2 dose of ZV in combination with R-GemOx or BR to evaluate efficacy
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Bendamustine
- Gemcitabine
- Oxaliplatin
- Rituximab
- Zilovertamab vedotin
Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Multiple myeloma
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
Merck Sharp & Dohme Corp.
Lead Sponsor
Chirfi Guindo
Merck Sharp & Dohme Corp.
Chief Medical Officer
Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme Corp.
Chief Executive Officer since 2021
J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University
Merck Sharp & Dohme LLC
Lead Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University