A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

Recruiting now · Phase 2/Phase 3

Conditions studied: DLBCL, Diffuse Large B-Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT05139017

Run by

Merck Sharp & Dohme LLC

People needed

290

Starts

2022-01-14

Expected to finish

2027-09-24

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Blue Ridge Cancer Care ( Site 0169) — Roanoke, Virginia, United States (enrolling)
• Hospital Aleman ( Site 2200) — Buenos Aites, Buenos Aires F.D., Argentina (enrolling)
• Beverly Hills Cancer Center ( Site 0184) — Beverly Hills, California, United States (enrolling)
• Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175) — Glendale, Arizona, United States (enrolling)
• Hospital Italiano de Buenos Aires ( Site 2203) — Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina (enrolling)
• BRP-Hialeah Hospital ( Site 0182) — Hialeah, Florida, United States (enrolling)
• Illinois Cancer Specialists ( Site 8000) — Niles, Illinois, United States (enrolling)
• Saint Elizabeth Medical Center Edgewood ( Site 0165) — Edgewood, Kentucky, United States (enrolling)
• Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163) — Boca Raton, Florida, United States (enrolling)
• Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133) — Louisville, Kentucky, United States (enrolling)
• Bass Medical Group ( Site 0166) — Walnut Creek, California, United States (enrolling)
• Dana-Farber Cancer Institute-Lymphoma ( Site 0111) — Boston, Massachusetts, United States (enrolling)
• University of Massachusetts Medical School ( Site 0119) — Worcester, Massachusetts, United States (enrolling)
• Corewell Health ( Site 0162) — Grand Rapids, Michigan, United States (enrolling)
• St. Vincent Frontier Cancer Center-Research ( Site 0108) — Billings, Montana, United States (enrolling)
• Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0188) — Grand Island, Nebraska, United States (enrolling)
• Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0177) — Omaha, Nebraska, United States (enrolling)
• Comprehensive Cancer Centers of Nevada ( Site 0168) — Las Vegas, Nevada, United States (enrolling)
• University of Kentucky Chandler Medical Center ( Site 0158) — Lexington, Kentucky, United States (enrolling)
• Presbyterian Rust Jorgensen Cancer ( Site 9506) — Rio Rancho, New Mexico, United States (enrolling)
• New York Medical College ( Site 0113) — Valhalla, New York, United States (enrolling)
• Alliance Cancer Specialists (ACS) ( Site 8001) — Horsham, Pennsylvania, United States (enrolling)
• Tennessee Cancer Specialists ( Site 7000) — Knoxville, Tennessee, United States (enrolling)
• Clermont Oncology Center ( Site 0174) — Clermont, Florida, United States (enrolling)
• Hospital Privado Universitario de Córdoba ( Site 2202) — Córdoba, Córdoba Province, Argentina (enrolling)

Full record on ClinicalTrials.gov

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