Clinical trial NCT05458297: A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
Official title: A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Follicular Lymphoma
Richter Transformation Lymphoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-07-14
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell lymphomas including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as monotherapy and in combination with respect to objective response rate.

* Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy
* Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy
* Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi
* Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy
* Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy

The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR).

As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)).


Eligibility criteria: The main inclusion criteria include, but are not limited to the following:

Inclusion Criteria:

* For aggressive B-cell malignancies mantle cell lymphoma (MCL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy.
* For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
* For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
* For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.

Exclusion Criteria:

* Has received solid organ transplant at any time.
* Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina (\<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
* Has pericardial effusion or clinically significant pleural effusion.
* Has ongoing Grade \>1 peripheral neuropathy.
* Has a demyelinating form of Charcot-Marie-Tooth disease.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
* Participants with FL who have transformed to a more aggressive type of lymphoma.
* Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) 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.
* 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.
* Active HBV or hepatitis C virus (HCV) infection.
* For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.

Primary outcomes:
measure: Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL with ≥1 Adverse Event (AE)
timeFrame: Up to approximately 57 months
measure: Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL who Discontinue from Study Therapy Due to AE
timeFrame: Up to approximately 57 months
measure: Percentage of Participants with MCL (Cohort C) who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Up to approximately 57 months
measure: Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E)
timeFrame: Up to approximately 57 months
measure: ORR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)
timeFrame: Up to approximately 57 months
measure: ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator in Participants with CLL
timeFrame: Up to approximately 57 months
Secondary outcomes:
measure: Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E)
timeFrame: Up to approximately 57 months
measure: DOR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)
timeFrame: Up to approximately 57 months
measure: DOR per iwCLL Criteria as Assessed by Investigator in Participants with CLL
timeFrame: Up to approximately 57 months
measure: Percentage of Participants with ≥1 AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)
timeFrame: Up to approximately 57 months
measure: Percentage of Participants Discontinuing from Study Therapy Due to AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)
timeFrame: Up to approximately 57 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology ( Site 0037)
state: Alaska
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 0040)
state: Arizona
city: Phoenix
country: United States
facility: Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008)
state: Colorado
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois ( Site 0031)
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics ( Site 0038)
state: Kansas
city: Saint Matthews
country: United States
facility: Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
state: Kentucky
city: Baltimore
country: United States
facility: Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center ( Site 0024)
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0018)
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute-Lymphoma ( Site 0026)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan ( Site 0009)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital ( Site 0035)
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 0023)
state: New York
city: Fargo
country: United States
facility: Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0014)
state: North Dakota
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0004)
state: Ohio
city: Sioux Falls
country: United States
facility: Avera Cancer Institute- Research ( Site 0011)
state: South Dakota
city: Spokane
country: United States
facility: Medical Oncology Associates, PS ( Site 0005)
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030)
state: Wisconsin
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN ( Site 0021)
state: Wisconsin
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1807)
state: Rio Grande Do Norte
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( Site 1809)
city: Sao Paulo
country: Brazil
facility: ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1808)
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano-Americas Oncologia ( Site 1805)
city: Vancouver
country: Canada
facility: BC Cancer Vancouver-Clinical Trials Unit ( Site 0201)
state: British Columbia
city: Moncton
country: Canada
facility: The Moncton Hospital-Oncology ( Site 0211)
state: New Brunswick
city: Halifax
country: Canada
facility: QEII Health Sciences Centre - Victoria General Site ( Site 0213)
state: Nova Scotia
city: London
country: Canada
facility: Lawson Health Research Institute - London Health Sciences Ce-London Regional Cancer Program ( Site 0203)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0202)
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre-Care Services ( Site 0208)
state: Saskatchewan
city: La Serena.
country: Chile
facility: IC La Serena Research ( Site 1909)
state: Coquimbo
city: Santiago.
country: Chile
facility: Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1907)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica Inmunocel ( Site 1910)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica Alemana de Santiago ( Site 1903)
state: Region M. De Santiago
city: Beijing
country: China
facility: Beijing Cancer hospital ( Site 1200)
state: Beijing
city: Guangzhou
country: China
facility: Zhujiang Hospital ( Site 1207)
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital ( Site 1202)
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center ( Site 1201)
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-hematology department ( Site 1212)
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1210)
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical,Science & Technology ( Site 1221)
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University-hematology department ( Site 1218)
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College ( Site 1223)
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University ( Site 1204)
state: Jiangxi
city: Nanchang
country: China
facility: Jiangxi Provincial Cancer Hospital ( Site 1213)
state: Jiangxi
city: Chuangchun
country: China
facility: Jilin Province Tumor Hospital-oncology department ( Site 1220)
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 1208)
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital of Sichuan University-Head and Neck Oncology ( Site 1206)
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University ( Site 1211)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 1214)
state: Zhejiang
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0300)
state: Brno-mesto
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava-Klinika Hematoonkologie ( Site 0301)
state: Moravskoslezsky Kraj
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0302)
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation ( Site 0401)
state: Harjumaa
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm. ( Site 0502)
state: Baden-Wurttemberg
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln ( Site 0506)
state: Nordrhein-Westfalen
city: Dublin
country: Ireland
facility: St. James's Hospital ( Site 0600)
city: Afula
country: Israel
facility: Emek Medical Center-Hematology Unit ( Site 0705)
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center-Hematology Department ( Site 0707)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Hematology and Bone Marrow Transplantation ( Site 0706)
city: Haifa
country: Israel
facility: Carmel Hospital ( Site 0709)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 0701)
city: Nahariya
country: Israel
facility: Galilee Medical Center ( Site 0710)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-Hemato Oncology ( Site 0700)
city: Bologna
country: Italy
facility: IRCCS - AOU di Bologna-SSD: Diagnosi e terapie dei linfomi e delle sindromi linfoproliferative cron ( Site 0800)
state: Emilia-Romagna
city: Rozzano
country: Italy
facility: Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0802)
state: Milano
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant ( Site 0803)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 0804)
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center ( Site 1108)
state: Aichi
city: Sapporo
country: Japan
facility: Hokkaido University Hospital ( Site 1104)
state: Hokkaido
city: Isehara
country: Japan
facility: Tokai University Hospital ( Site 1100)
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital ( Site 1106)
state: Miyagi
city: Sayama
country: Japan
facility: Kindai University Hospital ( Site 1102)
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital ( Site 1103)
state: Tokyo
city: Koto
country: Japan
facility: Cancer Institute Hospital of JFCR ( Site 1101)
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital ( Site 1105)
city: Okayama
country: Japan
facility: Okayama University Hospital ( Site 1107)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1300)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1301)
city: Arequipa
country: Peru
facility: Centro Medico Monte Carmelo ( Site 1702)
state: Ariqipa
city: Lima
country: Peru
facility: INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS ( Site 1700)
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 1008)
state: Lodzkie
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologiczny ( Site 1006)
state: Lubelskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow ( Site 1001)
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 1002)
state: Mazowieckie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S ( Site 1010)
state: Swietokrzyskie
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej MSWiA w Olsztynie-Oddzial Kliniczny Hematologii ( Site 1007)
state: Warminsko-mazurskie
city: Lisbon
country: Portugal
facility: Champalimaud Foundation ( Site 2002)
state: Lisboa
city: Braga
country: Portugal
facility: Unidade Local de Saude de Braga - Hospital de Braga ( Site 2001)
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 2000)
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore ( Site 1500)
state: Central Singapore
city: L'Hospitalet Del Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4003)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 4004)
state: Cataluna
city: Madrid
country: Spain
facility: MD Anderson Cancer Center ( Site 4006)
state: Madrid, Comunidad De
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra ( Site 4005)
state: Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca-Hematology ( Site 4001)
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund ( Site 5000)
state: Skane Lan
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 5002)
state: Uppsala Lan
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 5003)
state: Vastra Gotalands Lan
city: Stanbul
country: Turkey
facility: Mega Medipol-Hematology ( Site 6009)
state: Istanbul
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 6001)
city: Edirne
country: Turkey
facility: Trakya University ( Site 6005)
city: İzmir
country: Turkey
facility: Ege Universitesi Hastanesi ( Site 6002)
city: Samsun
country: Turkey
facility: Ondokuz Mayıs Universitesi-Oncology department ( Site 6004)
city: Truro
country: United Kingdom
facility: The Royal Cornwall Hospital-Haematology ( Site 7006)
state: Cornwall
city: London
country: United Kingdom
facility: University College London Hospital ( Site 7001)
state: London, City Of
city: Oxford
country: United Kingdom
facility: The Churchill Hospital ( Site 7002)
state: Oxfordshire
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust ( Site 7007)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: