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)

Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05139017
• Other study ID #: 2140-003
• Secondary ID: VLS-101MK-2140-0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 14, 2022
• Est. completion date: June 21, 2027

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: June 21, 2027
• Est. primary completion date: June 21, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 pericardial effusion or clinically significant 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 due 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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• DLBCL
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• 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

Drug:
• Gemcitabine
IV Infusion 1000 mg/m^2
• Oxaliplatin
IV Infusion 100 mg/m^2
• Bendamustine
IV Infusion 90 mg/m^2

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)	Toronto	Ontario
China	Beijing Cancer hospital ( Site 3000)	Beijing	Beijing
China	Chongqing University Cancer Hospital-Medical Oncology ( Site 3025)	Chongqing	Chongqing
China	Sun Yat-sen University Cancer Center-Internal Medicine ( Site 3001)	Guangzhou	Guangdong
China	Zhujiang Hospital ( Site 3002)	Guangzhou	Guangdong
China	Jiangxi Provincial Cancer Hospital ( Site 3005)	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University ( Site 3004)	Nanchang	Jiangxi
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 3017)	Wuhan	Hubei
France	Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700)	Paris
France	centre hospitalier lyon sud-Service Hématologie ( Site 0702)	Pierre-Bénite	Rhone
Israel	Emek Medical Center-Hematology Unit ( Site 1102)	Afula
Israel	Carmel Hospital ( Site 1103)	Haifa
Israel	Hadassah Medical Center ( Site 1100)	Jerusalem
Italy	IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1200)	Bologna
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1202)	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 1204)	Roma	Lazio
Italy	Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1203)	Rozzano	Milano
Korea, Republic of	Samsung Medical Center ( Site 0300)	Seoul
Korea, Republic of	Seoul National University Hospital-Oncology ( Site 0302)	Seoul
Poland	Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1302)	Gdynia	Pomorskie
Poland	Pratia MCM Krakow ( Site 1303)	Krakow	Malopolskie
Poland	Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologiczny ( Site 1304)	Lublin	Lubelskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Ukladu Chlonnego ( S	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site	Wroclaw	Dolnoslaskie
Thailand	Faculty of Medicine Siriraj Hospital-Division of Hematology, Department of Medicine ( Site 0400)	Bangkok	Krung Thep Maha Nakhon
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 0401)	Muang	Chiang Mai
Turkey	Ankara University Hospital Cebeci-hematology ( Site 1901)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 1902)	Bornova	Izmir
Turkey	Mega Medipol-Hematology ( Site 1909)	Istanbul
Turkey	Dokuz Eylül Üniversitesi-Hematology ( Site 1905)	Izmir
Turkey	Ondokuz Mayis Universitesi ( Site 1907)	Samsun
United Kingdom	University College London Hospital-Cancer Clinical Trials Unit ( Site 2100)	London-Camden	London, City Of
United States	University of Maryland ( Site 0123)	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center-Research ( Site 0108)	Billings	Montana
United States	Dana-Farber Cancer Institute-Lymphoma ( Site 0111)	Boston	Massachusetts
United States	Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)	Louisville	Kentucky
United States	Atlantic Health System ( Site 0116)	Morristown	New Jersey
United States	Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 0156)	Nashville	Tennessee
United States	Louisiana State University Health Sciences Center New Orleans ( Site 0134)	New Orleans	Louisiana
United States	New York Medical College ( Site 0113)	Valhalla	New York
United States	Innovative Clinical Research Institute ( Site 0122)	Whittier	California
United States	University of Massachusetts Medical School ( Site 0119)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Israel,  Italy,  Korea, Republic of,  Poland,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1	The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for Part 1 of this study.	Up to ~6 weeks
Primary	Number of participants who experienced an adverse event (AE)	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.	Up to ~34 months
Primary	Number of participants who discontinued study treatment due to an AE	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.	Up to ~34 months
Primary	PFS	PFS, defined as the time from randomization to the first documented disease progression per Lugano response criteria as assessed by BICR or death due to any cause, whichever occurs first will be presented.	Up to ~27 months
Secondary	Overall survival (OS)	OS, defined as the time from randomization to death due to any cause will be reported.	Up to ~34 months
Secondary	Objective response rate (ORR)	ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria as assessed by BICR will be presented.	Up to ~19 months
Secondary	Duration of response (DOR)	DOR, defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, will be reported.	Up to ~27 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary