A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05458297
• Other study ID #: 2140-006
• Secondary ID: MK-2140-006jRCT2
• Status: Recruiting
• Phase: Phase 2
• Start date: July 21, 2022
• Est. completion date: April 26, 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 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 - Cohort F: Participants with relapsed or refractory CLL 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 275
• Est. completion date: April 26, 2027
• Est. primary completion date: March 13, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Inclusion Criteria:

• For aggressive B-cell malignancies 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 FL and 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 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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Follicular Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Richter Transformation Lymphoma

Intervention

Biological:
• Zilovertamab vedotin
IV infusion

Drug:
• Nemtabrutinib
65 mg once daily (QD) orally

Locations

Country	Name	City	State
Brazil	Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1807)	Natal	Rio Grande Do Norte
Brazil	Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 (	Rio de Janeiro
Brazil	Hospital Paulistano-Americas Oncologia ( Site 1805)	Sao Paulo
Brazil	ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1808)	São Paulo	Sao Paulo
Canada	QEII Health Sciences Centre - Victoria General Site ( Site 0213)	Halifax	Nova Scotia
Canada	Lawson Health Research Institute - London Health Sciences Ce-London Regional Cancer Program ( Site 0	London	Ontario
Canada	The Moncton Hospital-Oncology ( Site 0211)	Moncton	New Brunswick
Canada	Jewish General Hospital ( Site 0202)	Montreal	Quebec
Canada	Allan Blair Cancer Centre-Care Services ( Site 0208)	Regina	Saskatchewan
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)	Toronto	Ontario
Canada	BC Cancer Vancouver-Clinical Trials Unit ( Site 0201)	Vancouver	British Columbia
Chile	IC La Serena Research ( Site 1909)	La Serena	Coquimbo
Chile	Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1907)	Santiago	Region M. De Santiago
Chile	Clínica Alemana de Santiago ( Site 1903)	Santiago	Region M. De Santiago
Chile	Clínica Inmunocel ( Site 1910)	Santiago	Region M. De Santiago
China	Beijing Cancer hospital ( Site 1200)	Beijing	Beijing
China	Jilin Province Tumor Hospital-oncology department ( Site 1220)	Changchun	Jilin
China	West China Hospital of Sichuan University-Head and Neck Oncology ( Site 1206)	Cheng Du	Sichuan
China	Southern Medical University Nanfang Hospital ( Site 1202)	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center ( Site 1201)	Guangzhou	Guangdong
China	Zhujiang Hospital ( Site 1207)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University ( Site 1211)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 1214)	Hangzhou	Zhejiang
China	Jiangxi Provincial Cancer Hospital ( Site 1213)	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University ( Site 1204)	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Center ( Site 1208)	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University-hematology department ( Site 1218)	Suzhou	Jiangsu
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 1221)	Wuhan	Hubei
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1210)	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical College ( Site 1223)	Xuzhou	Jiangsu
China	Henan Cancer Hospital-hematology department ( Site 1212)	Zhengzhou	Henan
Czechia	Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0300)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Ostrava-Klinika Hematoonkologie ( Site 0301)	Ostrava	Moravskoslezsky Kraj
Czechia	Vseobecna fakultni nemocnice v Praze-I. Interní klinika - klinika hematologie ( Site 0302)	Praha 2
Estonia	North Estonia Medical Centre Foundation ( Site 0401)	Tallinn	Harjumaa
Germany	Universitaetsklinikum Koeln ( Site 0506)	Köln	Nordrhein-Westfalen
Germany	Universitaetsklinikum Ulm ( Site 0502)	Ulm	Baden-Wurttemberg
Ireland	St. James's Hospital ( Site 0600)	Dublin
Israel	Emek Medical Center-Hematology Unit ( Site 0705)	Afula
Israel	Soroka Medical Center-Hematology Department ( Site 0707)	Be'er Sheva
Israel	Carmel Hospital ( Site 0709)	Haifa
Israel	Rambam Health Care Campus-Hematology and Bone Marrow Transplantation ( Site 0706)	Haifa
Israel	Hadassah Medical Center ( Site 0701)	Jerusalem
Israel	Sheba Medical Center-Hemato Oncology ( Site 0700)	Ramat Gan
Italy	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant	Alessandria
Italy	IRCCS - AOU di Bologna-SSD: Diagnosi e terapie dei linfomi e delle sindromi linfoproliferative cron	Bologna	Emilia-Romagna
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 0804)	Roma	Lazio
Italy	Humanitas-U.O di Oncologia medica ed Ematologia ( Site 0802)	Rozzano	Milano
Japan	National Cancer Center Hospital ( Site 1103)	Chuo-ku	Tokyo
Japan	Kyushu University Hospital ( Site 1105)	Fukuoka
Japan	Tokai University Hospital- Isehara Campus ( Site 1100)	Isehara	Kanagawa
Japan	Japanese Foundation for Cancer Research ( Site 1101)	Koto	Tokyo
Japan	National Hospital Organization Nagoya Medical Center ( Site 1108)	Nagoya	Aichi
Japan	Okayama University Hospital ( Site 1107)	Okayama
Japan	Kindai University Hospital- Osakasayama Campus ( Site 1102)	Osaka-sayama	Osaka
Japan	Hokkaido University Hospital ( Site 1104)	Sapporo	Hokkaido
Japan	Tohoku University Hospital ( Site 1106)	Sendai-shi	Miyagi
Korea, Republic of	Samsung Medical Center ( Site 1301)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1300)	Seoul
Peru	Centro Medico Monte Carmelo ( Site 1702)	Arequipa	Ariqipa
Peru	INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS ( Site 1700)	Lima
Poland	Pratia MCM Krakow ( Site 1001)	Krakow	Malopolskie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddial Hematologii Ogólnej ( Site 1008)	Lódz	Lodzkie
Poland	Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologiczny ( Site 1006)	Lublin	Lubelskie
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA w Olsztynie-Oddzial Kliniczny Hematologii ( Sit	Olsztyn	Warminsko-mazurskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Ukladu Chlonnego ( S	Warszawa	Mazowieckie
Portugal	2CA BRAGA ( Site 2001)	Braga
Portugal	Champalimaud Foundation ( Site 2002)	Lisbon	Lisboa
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 2000)	Porto
Singapore	National Cancer Centre Singapore ( Site 1500)	Singapore	Central Singapore
Spain	Hospital Universitari Vall d'Hebron ( Site 4004)	Barcelona	Cataluna
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4003)	L'Hospitalet Del Llobregat	Barcelona
Spain	Clinica Universidad de Navarra ( Site 4005)	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca-Hematology ( S	Salamanca
Sweden	Sahlgrenska Universitetssjukhuset ( Site 5003)	Gothenburg	Vastra Gotalands Lan
Sweden	Skånes Universitetssjukhus Lund ( Site 5000)	Lund	Skane Lan
Sweden	Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 5002)	Uppsala	Uppsala Lan
Turkey	Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 6001)	Ankara
Turkey	Trakya University ( Site 6005)	Edirne
Turkey	Ege Universitesi Hastanesi ( Site 6002)	Izmir
Turkey	Ondokuz Mayis Universitesi-Oncology department ( Site 6004)	Samsun
Turkey	Mega Medipol-Hematology ( Site 6009)	Stanbul	Istanbul
United Kingdom	University College London Hospital ( Site 7001)	London	England
United Kingdom	The Churchill Hospital ( Site 7002)	Oxford	Oxfordshire
United Kingdom	The Royal Cornwall Hospital-Haematology ( Site 7006)	Truro	Cornwall
United States	Alaska Oncology and Hematology ( Site 0037)	Anchorage	Alaska
United States	University of Michigan ( Site 0009)	Ann Arbor	Michigan
United States	University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008	Aurora	Colorado
United States	Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)	Baltimore	Maryland
United States	Dana-Farber Cancer Institute-Lymphoma ( Site 0026)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 0018)	Boston	Massachusetts
United States	Tufts Medical Center ( Site 0024)	Boston	Massachusetts
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C	Columbus	Ohio
United States	Cancer Care Specialists of Illinois ( Site 0031)	Decatur	Illinois
United States	Henry Ford Hospital ( Site 0035)	Detroit	Michigan
United States	University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics (	Fairway	Kansas
United States	Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0014)	Fargo	North Dakota
United States	University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030)	Madison	Wisconsin
United States	MEDICAL COLLEGE OF WISCONSIN ( Site 0021)	Milwaukee	Wisconsin
United States	Icahn School of Medicine at Mount Sinai ( Site 0023)	New York	New York
United States	Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)	Phoenix	Arizona
United States	Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)	Saint Matthews	Kentucky
United States	Avera Cancer Institute- Research ( Site 0011)	Sioux Falls	South Dakota
United States	Medical Oncology Associates, PS ( Site 0005)	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Chile,  China,  Czechia,  Estonia,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Peru,  Poland,  Portugal,  Singapore,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with =1 Adverse Event (AE) [cohort C and D]	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL, FL, and CLL who experienced an AE will be reported.	Up to approximately 57 months
Primary	Percentage of Participants Discontinuing from Study Therapy Due to AE (cohort C and D)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL, FL, and CLL who discontinued study treatment due to an AE will be reported.	Up to approximately 57 months
Primary	Percentage of Participants with Dose-Limiting Toxicity (DLT) [cohort C]	The Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 will be used to grade the severity of AEs. DLTs for participants with MCL as assessed by investigator will be reported.	Up to approximately 57 months
Primary	Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) [cohorts A, B, E and FL participants in D]	ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by BICR will be reported.	Up to approximately 57 months
Primary	ORR per Lugano Response Criteria as Assessed by Investigator (cohort C)	ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by investigator will be reported.	Up to approximately 57 months
Primary	ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator	ORR, defined as the percentage of participants who achieve a CR or PR per iwCLL criteria as assessed by investigator will be reported.	Up to approximately 57 months
Secondary	Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR (cohorts A, B, D (FL), and E)	DOR, defined as the time from the first documented evidence of CR or PR per Lugano Response Criteria as assessed by BICR, until disease progression or death due to any cause, whichever occurs first, will be reported.	Up to approximately 57 months
Secondary	DOR per Lugano Response Criteria as Assessed by Investigator (cohort C)	DOR, defined as the time from the first documented evidence of CR or PR per Lugano Response Criteria as assessed by investigator, until disease progression or death due to any cause, whichever occurs first, will be reported.	Up to approximately 57 months
Secondary	DOR per iwCLL Criteria as Assessed by Investigator (cohorts D [CLL] and F)	DOR, defined as the time from the first documented evidence of CR or PR per iwCLL criteria as assessed by investigator, until disease progression or death due to any cause, whichever occurs first, will be reported.	Up to approximately 57 months
Secondary	Percentage of Participants with =1 AE (cohorts A, B, E, and F)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL, RTL, FL, and CLL who experienced an AE will be reported.	Up to approximately 57 months
Secondary	Percentage of Participants Discontinuing from Study Therapy Due to AE (cohorts A, B, E, and F)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with MCL, RTL, FL, and CLL who discontinued study treatment due to an AE will be reported.	Up to approximately 57 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary