Clinical trial NCT05144841: A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Objective Response Rate (ORR) per Lugano Response Criteria
timeFrame: Up to approximately 50 months
Secondary outcomes:
measure: Duration of Response (DOR) per Lugano Response Criteria
timeFrame: Up to approximately 50 months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 50 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 50 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0229)
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute ( Site 0202)
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center ( Site 0204)
state: District of Columbia
city: Atlanta
country: United States
facility: Northside Hospital ( Site 0206)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center ( Site 0207)
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health ( Site 0225)
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland-Greenebaum Comprehensive Cancer Center ( Site 0211)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital-Cancer Center Protocol Office ( Site 0203)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 0200)
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute ( Site 0216)
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center ( Site 0209)
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health System Morristown Medical Center ( Site 0213)
state: New Jersey
city: Valhalla
country: United States
facility: New York Medical College ( Site 0215)
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0217)
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center ( Site 0222)
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C
state: Ohio
city: Pittsburgh
country: United States
facility: AHN West Penn Hospital ( Site 0212)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute- Research ( Site 0233)
state: South Dakota
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN ( Site 0234)
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0100)
state: Ontario
city: Temuco
country: Chile
facility: James Lind Centro de Investigación del Cáncer ( Site 2705)
state: Araucania
city: Santiago
country: Chile
facility: Clínica Alemana de Santiago ( Site 2704)
state: Region M. De Santiago
city: Beijing
country: China
facility: Beijing Cancer hospital ( Site 2900)
state: Beijing
city: Guangzhou
country: China
facility: SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 2907)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-hematology department ( Site 2903)
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital ( Site 2906)
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 2905)
state: Hunan
city: Changchun
country: China
facility: The First Hospital of Jilin University-Hematology ( Site 2910)
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 2908)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital ( Site 2902)
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital of Sichuan University-Head and Neck Oncology ( Site 2911)
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital-lymphoma ( Site 2901)
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University-Bone marrow transplant centre ( Site 2912)
state: Zhejiang
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0800)
state: Brno-mesto
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0801)
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation ( Site 0900)
state: Harjumaa
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque ( Site 1002)
state: Aquitaine
city: Paris
country: France
facility: Pitie Salpetriere University Hospital-Clinical haematology ( Site 1000)
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens ( Site 1214)
state: Attiki
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"-Hematology Department ( Site 1213)
state: Attiki
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center-Hematology Department ( Site 1403)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 1404)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 1402)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1400)
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa di Ematologia ( Site 1501)
state: Lombardia
city: Rozzano
country: Italy
facility: Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1503)
state: Milano
city: Bologna
country: Italy
facility: IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1500)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1502)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 0601)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0600)
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus ( Site 1601)
state: Hordaland
city: Oslo
country: Norway
facility: Oslo universitetssykehus, Radiumhospitalet ( Site 1600)
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site
state: Dolnoslaskie
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie-Oncology Department ( Site 1707)
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S
state: Mazowieckie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1702)
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia ( Site 1701)
state: Slaskie
city: L'Hospitalet Del Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 2002)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 2005)
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 2000)
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca ( Site 2003)
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund ( Site 2100)
state: Skane Lan
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset Solna ( Site 2102)
state: Stockholms Lan
city: Muang
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital ( Site 0702)
state: Chiang Mai
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 0701)
state: Krung Thep Maha Nakhon
city: Ankara
country: Turkey
facility: Ankara University Hospital Cebeci-hematology ( Site 2300)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi-Department of Hematology ( Site 2302)
city: Istanbul
country: Turkey
facility: Mega Medipol-Hematology ( Site 2308)
city: Izmir
country: Turkey
facility: Dokuz Eylül Üniversitesi-Hematology ( Site 2304)
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi ( Site 2306)
city: Trabzon
country: Turkey
facility: Karadeniz Teknik Universitesi Tip Fakultesi-Hematology ( Site 2307)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: