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NCT06150157PHASE1Recruiting

A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Janssen Research & Development, LLC

Start Date

12/20/2023

Completion Date

6/14/2028

Summary

The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D\[s\]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Be greater than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent * Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF) * Participants with ET and MF with risk characteristics as described in the protocol * Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (\<=) 2 * For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor Exclusion Criteria: * Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment * Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (\>=) 3 years after treatment ended are allowed to enter the study * Prior solid organ transplantation * Either of the following regarding hematopoietic stem cell transplantation: 1. Prior treatment with allogenic stem cell transplant less than or equal to (\<=) 6 months before the first dose of JNJ-88549968 or 2. Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy * History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment

Interventions

DRUG

JNJ-88549968

DRUG

Ruxolitinib

DRUG

Momelotinib

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Conditions

Neoplasms

Locations

City of Hope

Duarte, California 91010

United States

UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center

Aurora, Colorado 80045

United States

Moffit Cancer center

Tampa, Florida 33612

United States

Emory University

Atlanta, Georgia 30322

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Start Midwest

Grand Rapids, Michigan 49546

United States

START New Jersey

East Brunswick, New Jersey 08816

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Levine Cancer Institute

Charlotte, North Carolina 28204

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Sarah Cannon Cancer Institute

Nashville, Tennessee 37203

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario M5G 1Z5

Canada

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

Peking Union Medical College Hospital

Beijing, 100032

China

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 301617

China

Hopital Saint Louis

Paris, 75475

France

CH LYON SUD - Hematology

Pierre-Bénite, 69495

France

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059

France

Universitaetsklinikum der RWTH Aachen

Aachen, 52074

Germany

Charite Campus Benjamin Franklin

Berlin, 12203

Germany

Med. Universitatsklinik Essen

Essen, 45147

Germany

Medizinische Hochschule Hannover

Hanover, 30625

Germany

Universitaetsklinikum Heidelberg

Heidelberg, 69120

Germany

Universitaetsklinikum Regensburg

Regensburg, 93053

Germany

Carmel Medical Center

Haifa, 3436212

Israel

Hadassah University Hospita Ein Kerem

Jerusalem, 9112001

Israel

Sheba Medical Center

Ramat Gan, 5266202

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239

Israel

Policlinico Sant'Orsola Malpighi

Bologna, 40138

Italy

Policlinico di Milano

Milan, 21022

Italy

Juntendo University Hospital

Bunkyō City, 113 8431

Japan

National Cancer Center Hospital East

Kashiwa, 277 8577

Japan

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916

Spain

Hosp. Clinico Univ. de Valencia

Valencia, 46010

Spain

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG

United Kingdom

Guy's and St Thomas' Hospital

London, SE1 9RT

United Kingdom

Churchill Hospital

Oxford, OX3 7LE

United Kingdom