Treatment of CALR-Mutated Myeloproliferative Neoplasms with JNJ-88549968

A First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-88549968, a T-cell Redirecting Bispecific Antibody for CALR-mutated Myeloproliferative Neoplasms

This study is testing a new treatment called JNJ-88549968 to see if it is safe and effective for people with CALR-mutated myeloproliferative neoplasms.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Janssen Research & Development, LLC (Industry-sponsored)
• Drugs / interventions: ruxolitinib, momelotinib
• Locations: 31 sites (Duarte, California and 30 other locations)
• Trial ID: NCT06150157 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and determine the recommended Phase 2 dose of JNJ-88549968 for patients with calreticulin (CALR)-mutated myeloproliferative neoplasms. The trial consists of two parts: a dose escalation phase to identify optimal dosing schedules and a cohort expansion phase to further assess safety at the recommended doses. Participants will be monitored for adverse effects and treatment efficacy throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed CALR driver mutation and specific risk characteristics associated with essential thrombocythemia or myelofibrosis.

Not a fit: Patients with known allergies to the study treatment or concurrent malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with CALR-mutated myeloproliferative neoplasms.

How similar studies have performed: While this approach is novel in targeting CALR mutations specifically, similar studies in myeloproliferative neoplasms have shown promising results.

Eligibility criteria

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

Where this trial is running

Duarte, California and 30 other locations

• City of Hope — Duarte, California, United States (Recruiting)
• UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center — Aurora, Colorado, United States (Recruiting)
• Moffit Cancer center — Tampa, Florida, United States (Recruiting)
• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Montefiore Medical Center — The Bronx, New York, United States (Recruiting)
• Levine Cancer Institute — Charlotte, North Carolina, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• Sarah Cannon Cancer Institute — Nashville, Tennessee, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Princess Margaret Cancer Centre University Health Network — Toronto, Ontario, Canada (Recruiting)
• Jewish General Hospital — Montreal, Quebec, Canada (Recruiting)
• Hopital Saint Louis — Paris, France (Recruiting)
• CH LYON SUD - Hematology — Pierre-Bénite, France (Recruiting)
• Universitaetsklinikum der RWTH Aachen — Aachen, Germany (Recruiting)
• Charite Campus Benjamin Franklin — Berlin, Germany (Recruiting)
• Med. Universitatsklinik Essen — Essen, Germany (Recruiting)
• Medizinische Hochschule Hannover — Hanover, Germany (Recruiting)
• Universitaetsklinikum Heidelberg — Heidelberg, Germany (Recruiting)
• Universitaetsklinikum Regensburg — Regensburg, Germany (Recruiting)
• Carmel Medical Center — Haifa, Israel (Recruiting)
• Hadassah University Hospita Ein Kerem — Jerusalem, Israel (Recruiting)
• Sheba Medical Center — Ramat Gan, Israel (Recruiting)
• Tel Aviv Sourasky Medical Center — Tel Aviv, Israel (Recruiting)
• Policlinico Sant'Orsola Malpighi — Bologna, Italy (Recruiting)
• Policlinico di Milano — Milan, Italy (Recruiting)
• Hosp. Univ. Germans Trias I Pujol — Badalona, Spain (Recruiting)
• Hosp. Clinico Univ. de Valencia — Valencia, Spain (Recruiting)
• University College London Hospitals Nhs Foundation Trust — London, United Kingdom (Recruiting)
• Guy's and St Thomas' Hospital — London, United Kingdom (Recruiting)
• Churchill Hospital — Oxford, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Study Contact

Conditions Neoplasms