Recruiting
Phase 2
Phase 3

Zilovertamab Vedotin & Standard of Care

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT05139017

Conditions

DLBCL

Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zilovertamab vedotin

Rituximab

Gemcitabine

Oxaliplatin

Bendamustine

Study Details

Brief summary:

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.

Conditions

DLBCL

Diffuse Large B-Cell Lymphoma

Study ID

NCT05139017

Start date

Jan 14, 2022

Status verified date

Sep, 2026

Completion date

Sep 24, 2027

Anticipated

Primary completion date

Sep 24, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).
  • Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator.
  • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation.
  • Has adequate organ function.
  • Is able to provide new or archival tumor tissue sample not previously irradiated.

Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:

  • Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy.
  • Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy.

Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:

  • Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy.
  • Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.

Exclusion Criteria:

  • Not applicable with protocol amendment 4: Has history of transformation of indolent disease to DLBCL
  • Has received solid organ transplant at any time.
  • Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL).
  • Has clinically significant (ie, active) cardiovascular disease or serious cardiac arrhythmia requiring medication.
  • Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD.
  • Has clinically significant pericardial or pleural effusion.
  • Has ongoing Grade >1 peripheral neuropathy.
  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  • Has a demyelinating form of Charcot-Marie-Tooth disease.
  • Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction.
  • Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
  • Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Has ongoing corticosteroid therapy.
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
  • Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known active Hepatitis C virus infection.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Study Design

Enrollment

290 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: ZV + R-GemOx (Part 1)

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.

experimental: ZV + R-GemOx (Part 2)

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.

active comparator: R-GemOx (active control for Part 2)

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.

experimental: ZV + BR (Part 2)

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.

active comparator: Bendamustine Rituximab (BR)

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.

experimental: ZV + BR (Part 1)

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.

Interventions

Zilovertamab vedotin

Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg

Rituximab

IV Infusion 375 mg/m\^2

Gemcitabine

IV Infusion 1000 mg/m\^2

Oxaliplatin

IV Infusion 100 mg/m\^2

Bendamustine

IV Infusion 90 mg/m\^2

Granulocyte Colony-Stimulating Factor (G-CSF)

Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.

Primary outcome measure

  • Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1 [ Time Frame: Up to ~6 weeks ]
  • Number of participants who experienced an adverse event (AE) [ Time Frame: Up to ~68 months ]
  • Number of participants who discontinued study treatment due to an AE [ Time Frame: Up to ~68 months ]
  • Overall survival (OS) [ Time Frame: Up to ~35 months ]
  • Progression-free survival (PFS) [ Time Frame: Up to ~35 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175)

Recruiting

Glendale, Arizona, United States, 85304

Contacts

Study Coordinator

602-978-6255

Bass Medical Group ( Site 0166)

Recruiting

Walnut Creek, California, United States, 94598

Contacts

Study Coordinator

925-433-8786

Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163)

Recruiting

Boca Raton, Florida, United States, 33486

Contacts

Study Coordinator

561-955-4145

Clermont Oncology Center ( Site 0174)

Recruiting

Clermont, Florida, United States, 34711

Contacts

Study Coordinator

352-242-1366

BRP-Hialeah Hospital ( Site 0182)

Recruiting

Hialeah, Florida, United States, 33013

Contacts

Study Coordinator

833-489-4968

Illinois Cancer Specialists ( Site 8000)

Recruiting

Niles, Illinois, United States, 60714

Contacts

Study Coordinator

847-827-9060

Saint Elizabeth Medical Center Edgewood ( Site 0165)

Recruiting

Edgewood, Kentucky, United States, 41017

Contacts

Study Coordinator

859-301-2000

University of Kentucky Chandler Medical Center ( Site 0158)

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Study Coordinator

859-257-3379

Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)

Recruiting

Louisville, Kentucky, United States, 40207

Contacts

Study Coordinator

502-629-3681

Corewell Health ( Site 0162)

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Study Coordinator

616-486-6180

St. Vincent Frontier Cancer Center-Research ( Site 0108)

Recruiting

Billings, Montana, United States, 59102

Contacts

Study Coordinator

406-238-6290

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0188)

Recruiting

Grand Island, Nebraska, United States, 68803

Contacts

Study Coordinator

402-334-4773

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0177)

Recruiting

Omaha, Nebraska, United States, 68130

Contacts

Study Coordinator

402-334-4773

Comprehensive Cancer Centers of Nevada ( Site 0168)

Recruiting

Las Vegas, Nevada, United States, 89169

Contacts

Study Coordinator

702-952-3400

New York Medical College ( Site 0113)

Recruiting

Valhalla, New York, United States, 10595

Contacts

Study Coordinator

914-594-2150

Alliance Cancer Specialists (ACS) ( Site 8001)

Recruiting

Horsham, Pennsylvania, United States, 19044

Contacts

Study Coordinator

215-706-4176

Tennessee Cancer Specialists ( Site 7000)

Recruiting

Knoxville, Tennessee, United States, 37909

Contacts

Study Coordinator

865-862-0998

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-03.