A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004)

Relapsed or Refractory Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

A Phase 2 Open-label Clinical Study to Evaluate the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-004)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05144841
• Other study ID #: 2140-004
• Secondary ID: MK-2140-0042021-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 8, 2022
• Est. completion date: June 10, 2025

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate zilovertamab vedotin with respect to objective response rate and duration of response per Lugano Response Criteria as assessed by blinded independent central review (BICR). Safety and tolerability will also be evaluated in this Phase 2, single arm, interventional study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. completion date: June 10, 2025
• Est. primary completion date: June 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has relapsed or refractory (rr) DLBCL; has progressed after at least 2 lines of prior therapy; and has progressed after auto- stem cell transplant (SCT) or are auto-SCT ineligible. Must have received prior multiagent regimen that includes an alkylating agent. anthracycline, and anti-CD20 (cluster of differentiation 20) monoclonal antibody.
• Has histologically confirmed diagnosis of DLBCL.
• Has radiographically measurable DLBCL per the Lugano Response Criteria.
• Should either be post- chimeric antigen receptor T cell therapy (CAR-T) failure or ineligible for CAR-T (for any reason).
• Life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before time of enrollment.
• Has adequate organ function.

Exclusion Criteria:

• Has received a diagnosis of Primary mediastinal B-cell lymphoma (PMBCL).
• Has undergone solid organ transplant at any time.
• Has a history of any clinically significant cardiovascular conditions within 6 months of screening or serious cardiac arrhythmia requiring medication.
• Has known history of liver cirrhosis.
• 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.
• Transformed DLBCL from indolent lymphoma.
• In participants with prior allo-SCT, acute graft versus host disease (GVHD) or ongoing evidence of chronic GVHD.
• 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 28 days of start of study intervention. Participants. must have recovered from all radiation-related toxicities.
• Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent).
• 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.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of hepatitis B or known active hepatitis C virus (HCV).

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Intervention

Biological:
• MK-2140 (zilovertamab vedotin)
IV infusion of 2.5 mg/kg
• MK-2140 (zilovertamab vedotin)
IV infusion of 2.25 mg/kg

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0100)	Toronto	Ontario
Chile	Clínica Alemana de Santiago ( Site 2704)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 2705)	Temuco	Araucania
China	Beijing Cancer hospital ( Site 2900)	Beijing	Beijing
China	The First Hospital of Jilin University-Hematology ( Site 2910)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 2905)	Changsha	Hunan
China	West China Hospital of Sichuan University-Head and Neck Oncology ( Site 2911)	Cheng Du	Sichuan
China	SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 2907)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University-Bone marrow transplant centre ( Site 2912)	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center ( Site 2908)	Shanghai	Shanghai
China	Shanghai East Hospital ( Site 2902)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute and Hospital-lymphoma ( Site 2901)	Tianjin	Tianjin
China	Wuhan Union Hospital ( Site 2906)	Wuhan	Hubei
China	Henan Cancer Hospital-hematology department ( Site 2903)	Zhengzhou	Henan
Czechia	Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0800)	Brno	Brno-mesto
Czechia	Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0801)	Praha 2
Estonia	North Estonia Medical Centre Foundation ( Site 0900)	Tallinn	Harjumaa
France	Centre Hospitalier de la Côte Basque ( Site 1002)	Bayonne	Aquitaine
France	Pitie Salpetriere University Hospital-Clinical haematology ( Site 1000)	Paris
Greece	Evangelismos General Hospital of Athens ( Site 1214)	Athens	Attiki
Greece	General Hospital of Athens "Laiko"-Hematology Department ( Site 1213)	Athens	Attiki
Israel	Soroka Medical Center-Hematology Department ( Site 1403)	Be'er Sheva
Israel	Hadassah Medical Center ( Site 1402)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 1404)	Jerusalem
Israel	Sourasky Medical Center ( Site 1400)	Tel Aviv
Italy	IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1500)	Bologna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa di Ematologia ( Site 1501)	Milan	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1502)	Napoli
Italy	Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1503)	Rozzano	Milano
Korea, Republic of	Samsung Medical Center ( Site 0600)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0601)	Seoul
Norway	Haukeland Universitetssjukehus ( Site 1601)	Bergen	Hordaland
Norway	Oslo universitetssykehus, Radiumhospitalet ( Site 1600)	Oslo
Poland	Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1702)	Gdynia	Pomorskie
Poland	Pratia Onkologia ( Site 1701)	Katowice	Slaskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1707)	Kraków	Malopolskie
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
Spain	Hospital Universitari Vall d'Hebron ( Site 2005)	Barcelona
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 2002)	L'Hospitalet Del Llobregat	Barcelona
Spain	Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 2000)	Madrid
Spain	Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 2003)	Salamanca
Sweden	Skånes Universitetssjukhus Lund ( Site 2100)	Lund	Skane Lan
Sweden	Karolinska Universitetssjukhuset Solna ( Site 2102)	Solna	Stockholms Lan
Thailand	Faculty of Medicine Siriraj Hospital ( Site 0701)	Bangkok	Krung Thep Maha Nakhon
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 0702)	Muang	Chiang Mai
Turkey	Ankara University Hospital Cebeci-hematology ( Site 2300)	Ankara
Turkey	Hacettepe Universitesi-Department of Hematology ( Site 2302)	Ankara
Turkey	Mega Medipol-Hematology ( Site 2308)	Istanbul
Turkey	Dokuz Eylül Üniversitesi-Hematology ( Site 2304)	Izmir
Turkey	Ondokuz Mayis Universitesi ( Site 2306)	Samsun
Turkey	Karadeniz Teknik Universitesi Tip Fakultesi-Hematology ( Site 2307)	Trabzon
United States	University of Michigan ( Site 0200)	Ann Arbor	Michigan
United States	Northside Hospital ( Site 0206)	Atlanta	Georgia
United States	University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0211)	Baltimore	Maryland
United States	Massachusetts General Hospital-Cancer Center Protocol Office ( Site 0203)	Boston	Massachusetts
United States	University of Chicago Medical Center ( Site 0207)	Chicago	Illinois
United States	University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0217)	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center ( Site 0222)	Cleveland	Ohio
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C	Columbus	Ohio
United States	Karmanos Cancer Institute ( Site 0216)	Detroit	Michigan
United States	Franciscan St. Francis Health ( Site 0225)	Indianapolis	Indiana
United States	MEDICAL COLLEGE OF WISCONSIN ( Site 0234)	Milwaukee	Wisconsin
United States	Atlantic Health System Morristown Medical Center ( Site 0213)	Morristown	New Jersey
United States	St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0229)	Orange	California
United States	AHN West Penn Hospital ( Site 0212)	Pittsburgh	Pennsylvania
United States	Saint Louis University Cancer Center ( Site 0209)	Saint Louis	Missouri
United States	Avera Cancer Institute- Research ( Site 0233)	Sioux Falls	South Dakota
United States	New York Medical College ( Site 0215)	Valhalla	New York
United States	Georgetown University Medical Center ( Site 0204)	Washington	District of Columbia
United States	Innovative Clinical Research Institute ( Site 0202)	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Chile,  China,  Czechia,  Estonia,  France,  Greece,  Israel,  Italy,  Korea, Republic of,  Norway,  Poland,  Spain,  Sweden,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per Lugano Response Criteria	ORR is percentage of participants with complete response (CR) or partial response (PR). ORR by cohort, relapsed or refractory (rr) DLBCL as assessed by BICR according to Lugano Response Criteria 2014 in participants treated with zilovertamab vedotin Q3W. CR is the complete radiologic response. PR is a partial response, >=50% decrease in sum of the product of the perpendicular diameters for multiple lesions for up to 6 target measurable nodes and extranodal sites.	Up to approximately 50 months
Secondary	Duration of Response (DOR) per Lugano Response Criteria	Duration of Response (DOR) is time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 50 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.	Up to approximately 50 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 50 months

External Links

•   Merck Oncology Clinical Trials Information
•   Plain Language Summary