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

Phase 2

Active, not recruiting

• Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma
• Interventions: Biological: MK-2140 (zilovertamab vedotin)

• Registration Number: NCT05144841
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-22
• Study First Submitted QC: 2021-11-22
• Study First Posted: 2021-12-03
• Study Start: 2022-01-08
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Primary Completion: 2025-06-10
• Study Completion: 2025-06-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 140

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	MK-2140 (zilovertamab vedotin)	Participants will receive treatment with zilovertamab vedotin 2.5 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.
Arm B	MK-2140 (zilovertamab vedotin)	Participants will receive treatment with zilovertamab vedotin 2.25 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks (Q3W)) until documented disease progression or any other discontinuation criterion is met.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) per Lugano Response Criteria	Up to approximately 50 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Experience an Adverse Event (AE)	Up to approximately 50 months	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.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 50 months	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.
Duration of Response (DOR) per Lugano Response Criteria	Up to approximately 50 months	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.

Trial Locations

Locations (71)

Centre Hospitalier de la Côte Basque ( Site 1002); 🇫🇷 Bayonne, Aquitaine, France

Skånes Universitetssjukhus Lund ( Site 2100); 🇸🇪 Lund, Skane Lan, Sweden

Ankara University Hospital Cebeci-hematology ( Site 2300); 🇹🇷 Ankara, Turkey

Ondokuz Mayıs Universitesi ( Site 2306); 🇹🇷 Samsun, Turkey

Pitie Salpetriere University Hospital-Clinical haematology ( Site 1000); 🇫🇷 Paris, France

Shaare Zedek Medical Center ( Site 1404); 🇮🇱 Jerusalem, Israel

Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 2002); 🇪🇸 L'Hospitalet Del Llobregat, Barcelona, Spain

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0601); 🇰🇷 Seoul, Korea, Republic of

Evangelismos General Hospital of Athens ( Site 1214); 🇬🇷 Athens, Attiki, Greece

Hacettepe Universitesi-Department of Hematology ( Site 2302); 🇹🇷 Ankara, Turkey

Hospital Universitari Vall d'Hebron ( Site 2005); 🇪🇸 Barcelona, Spain

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 2003); 🇪🇸 Salamanca, Spain

Haukeland Universitetssjukehus ( Site 1601); 🇳🇴 Bergen, Hordaland, Norway

Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 2000); 🇪🇸 Madrid, Spain

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1503); 🇮🇹 Rozzano, Milano, Italy

IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1500); 🇮🇹 Bologna, Italy

Karadeniz Teknik Universitesi Tip Fakultesi-Hematology ( Site 2307); 🇹🇷 Trabzon, Turkey

Samsung Medical Center ( Site 0600); 🇰🇷 Seoul, Korea, Republic of

Mega Medipol-Hematology ( Site 2308); 🇹🇷 Istanbul, Turkey

St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0229); 🇺🇸 Orange, California, United States

Innovative Clinical Research Institute ( Site 0202); 🇺🇸 Whittier, California, United States

Georgetown University Medical Center ( Site 0204); 🇺🇸 Washington, District of Columbia, United States

Northside Hospital ( Site 0206); 🇺🇸 Atlanta, Georgia, United States

University of Chicago Medical Center ( Site 0207); 🇺🇸 Chicago, Illinois, United States

University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0211); 🇺🇸 Baltimore, Maryland, United States

Karmanos Cancer Institute ( Site 0216); 🇺🇸 Detroit, Michigan, United States

University of Michigan ( Site 0200); 🇺🇸 Ann Arbor, Michigan, United States

Saint Louis University Cancer Center ( Site 0209); 🇺🇸 Saint Louis, Missouri, United States

Atlantic Health System Morristown Medical Center ( Site 0213); 🇺🇸 Morristown, New Jersey, United States

New York Medical College ( Site 0215); 🇺🇸 Valhalla, New York, 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

AHN West Penn Hospital ( Site 0212); 🇺🇸 Pittsburgh, Pennsylvania, United States

Avera Cancer Institute- Research ( Site 0233); 🇺🇸 Sioux Falls, South Dakota, United States

MEDICAL COLLEGE OF WISCONSIN ( Site 0234); 🇺🇸 Milwaukee, Wisconsin, United States

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0100); 🇨🇦 Toronto, Ontario, Canada

Beijing Cancer hospital ( Site 2900); 🇨🇳 Beijing, Beijing, China

SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 2907); 🇨🇳 Guangzhou, Guangdong, China

Henan Cancer Hospital-hematology department ( Site 2903); 🇨🇳 Zhengzhou, Henan, China

Tianjin Medical University Cancer Institute and Hospital-lymphoma ( Site 2901); 🇨🇳 Tianjin, Tianjin, China

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, Czechia

North Estonia Medical Centre Foundation ( Site 0900); 🇪🇪 Tallinn, Harjumaa, Estonia

Franciscan St. Francis Health ( Site 0225); 🇺🇸 Indianapolis, Indiana, United States

Massachusetts General Hospital-Cancer Center Protocol Office ( Site 0203); 🇺🇸 Boston, Massachusetts, United States

University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0217); 🇺🇸 Cincinnati, Ohio, United States

Hunan Cancer Hospital ( Site 2905); 🇨🇳 Changsha, Hunan, China

The First Hospital of Jilin University-Hematology ( Site 2910); 🇨🇳 Changchun, Jilin, China

Fudan University Shanghai Cancer Center ( Site 2908); 🇨🇳 Shanghai, Shanghai, China

Wuhan Union Hospital ( Site 2906); 🇨🇳 Wuhan, Hubei, China

Shanghai East Hospital ( Site 2902); 🇨🇳 Shanghai, Shanghai, China

West China Hospital of Sichuan University-Head and Neck Oncology ( Site 2911); 🇨🇳 Cheng Du, Sichuan, China

The First Affiliated Hospital, Zhejiang University-Bone marrow transplant centre ( Site 2912); 🇨🇳 Hangzhou, Zhejiang, China

James Lind Centro de Investigación del Cáncer ( Site 2705); 🇨🇱 Temuco, Araucania, Chile

Soroka Medical Center-Hematology Department ( Site 1403); 🇮🇱 Be'er Sheva, Israel

Sourasky Medical Center ( Site 1400); 🇮🇱 Tel Aviv, Israel

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S; 🇵🇱 Warszawa, Mazowieckie, Poland

Faculty of Medicine Siriraj Hospital ( Site 0701); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

General Hospital of Athens "Laiko"-Hematology Department ( Site 1213); 🇬🇷 Athens, Attiki, Greece

Hadassah Medical Center ( Site 1402); 🇮🇱 Jerusalem, Israel

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1707); 🇵🇱 Kraków, Malopolskie, 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

Clínica Alemana de Santiago ( Site 2704); 🇨🇱 Santiago, Region M. De Santiago, Chile

Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site; 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Maharaj Nakorn Chiang Mai Hospital ( Site 0702); 🇹🇭 Muang, Chiang Mai, Thailand

Oslo universitetssykehus, Radiumhospitalet ( Site 1600); 🇳🇴 Oslo, Norway

Karolinska Universitetssjukhuset Solna ( Site 2102); 🇸🇪 Solna, Stockholms Lan, Sweden

Dokuz Eylül Üniversitesi-Hematology ( Site 2304); 🇹🇷 Izmir, Turkey

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