290 Participants Needed

Zilovertamab Vedotin + Standard of Care for Diffuse Large B-Cell Lymphoma

Recruiting at 86 trial locations
TF
Overseen ByToll Free Number
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

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?

Zilovertamab Vedotin is unique because it combines an antibody-drug conjugate with standard chemotherapy drugs, potentially offering a new option for patients with relapsed or refractory diffuse large B-cell lymphoma who have limited treatment choices.1361011

Research Team

MD

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

I can provide a new or stored tumor sample that hasn't been exposed to radiation.
My previous CAR-T cell therapy did not work, or I am not eligible for it.
My DLBCL is measurable by scans according to Lugano criteria.
See 6 more

Exclusion Criteria

I have an active Hepatitis C infection.
My slow-growing cancer has changed into aggressive large B-cell lymphoma.
I have a type of Charcot-Marie-Tooth disease that affects the nerve covering.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation (Part 1)

Participants receive ZV in combination with R-GemOx or BR to confirm the dose

Up to 6 cycles of 21 days each
1 visit per cycle (in-person)

Efficacy Expansion (Part 2)

Participants receive the recommended Phase 2 dose of ZV in combination with R-GemOx or BR to evaluate efficacy

Up to 6 cycles of 21 days each
1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 26 months

Treatment Details

Interventions

  • Bendamustine
  • Gemcitabine
  • Oxaliplatin
  • Rituximab
  • Zilovertamab vedotin
Trial OverviewThe trial is testing Zilovertamab Vedotin (ZV) combined with standard care options against just the standard care for rrDLBCL treatment. It's in two parts: first confirming the dose of ZV and then expanding to test its effectiveness. The goal is to see if adding ZV improves progression-free survival compared to the current treatments alone.
Participant Groups
6Treatment groups
Experimental Treatment
Active Control
Group I: ZV + R-GemOx (Part 2)Experimental Treatment5 Interventions
Using the recommended Phase 2 dose (RP2D) dose of ZV plus R-GemOx from Part 1, participants will receive ZV plus R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Group II: ZV + R-GemOx (Part 1)Experimental Treatment5 Interventions
Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Gemcitabine 1000 mg/m\^2 and Oxaliplatin 100 mg/m\^2 (R-GemOx) given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.
Group III: ZV + BR (Part 2)Experimental Treatment4 Interventions
Using RP2D from Part 1, participants will receive ZV plus Rituximab 375 mg/m\^2, given intravenously on Day 1 and Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2, of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Group IV: ZV + BR (Part 1)Experimental Treatment4 Interventions
Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Bendamustine 90 mg/m\^2 (BR) given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.
Group V: R-GemOx (active control for Part 2)Active Control3 Interventions
Participants will receive R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Group VI: Bendamustine Rituximab (BR)Active Control2 Interventions
Participants will receive Rituximab 375 mg/m\^2, given intravenously on Day 1 Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸
Approved in United States as Treanda for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
🇪🇺
Approved in European Union as Ribomustin for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
  • Multiple myeloma
🇨🇦
Approved in Canada as Levact for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
🇯🇵
Approved in Japan as Bendamustine hydrochloride for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials
2,287
Recruited
4,582,000+
Chirfi Guindo profile image

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 profile image

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

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

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 profile image

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

Findings from Research

In a study of 28 Chinese patients with relapse/refractory diffuse large B-cell lymphoma (R/R DLBCL) who were ineligible for transplantation, the polatuzumab vedotin (pola) combined with rituximab and bendamustine (pola-BR) regimen showed a promising overall response rate of 71.4% and a complete response rate of 25.0%.
The estimated median progression-free survival (PFS) was 200 days, with manageable safety profiles as high-grade peripheral neuropathy was not observed, although common adverse events included thrombocytopenia and neutropenia.
A retrospective cohort study of polatuzumab vedotin combined with immunochemotherapy in Chinese patients with relapse/refractory diffuse large B cell lymphoma.Liu, Y., Wuxiao, Z., Kong, F., et al.[2022]
Rituximab plus bendamustine (R-B) is less toxic and achieves similar complete remission rates compared to R-CHOP in patients with follicular lymphoma grade 3A, with 97% vs. 96% complete remissions respectively.
Patients treated with R-B experienced significantly lower relapse rates (16% vs. 41%) and longer progression-free survival (15 years vs. 11.7 years) compared to those treated with R-CHOP, making R-B a more effective first-line treatment option.
Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study.Mondello, P., Steiner, N., Willenbacher, W., et al.[2019]
Brentuximab vedotin (Bv) combined with bendamustine (B) showed a high overall response rate of 79% and a complete response rate of 49% in 47 patients with relapsed or refractory classic Hodgkin lymphoma, indicating its efficacy as a treatment option.
The treatment resulted in a median progression-free survival of 18 months and a 2-year overall survival rate of 72%, particularly benefiting patients who achieved a major clinical response and those who underwent stem cell transplantation afterward.
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study.Iannitto, E., Romano, A., Scalzulli, PR., et al.[2021]

References

A retrospective cohort study of polatuzumab vedotin combined with immunochemotherapy in Chinese patients with relapse/refractory diffuse large B cell lymphoma. [2022]
Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. [2019]
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]
Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. [2021]
Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas. [2021]
Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. [2021]
Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma. [2015]
Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey. [2023]
Optimal use of bendamustine in hematologic disorders: Treatment recommendations from an international consensus panel - an update. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]
Polatuzumab vedotin-based salvage immunochemotherapy as third-line or beyond treatment for patients with diffuse large B-cell lymphoma: a real-world experience. [2022]