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

Purpose

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.

Condition

  • Neoplasms

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only) 		In dose escalation (Part 1), participants will receive JNJ-88549968. For myelofibrosis (MF) participants only, the study will explore a Phase 1b cohort in which the janus kinase (JAK) inhibitor ruxolitinib or momelotinib is started in combination with JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule (s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. In dose expansion (Part 2, Part 2b [US only]), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1, Part 1b [US only]).
  • Drug: JNJ-88549968
    JNJ-88549968 will be administered.
  • Drug: Ruxolitinib
    For US sites: Ruxolitinib will be administered for participants with MF only.
  • Drug: Momelotinib
    For US sites: Momelotinib will be administered for participants with MF only.

Recruiting Locations

City of Hope
Duarte, California 91010

UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
Aurora, Colorado 80045

Moffit Cancer center
Tampa, Florida 33612

Emory University
Atlanta, Georgia 30322

University of Michigan
Ann Arbor, Michigan 48109

Memorial Sloan Kettering Cancer Center
New York, New York 10065

Montefiore Medical Center
The Bronx, New York 10467

Levine Cancer Institute
Charlotte, North Carolina 28204

University of Pennsylvania
Philadelphia, Pennsylvania 19104

Sarah Cannon Cancer Institute
Nashville, Tennessee 37203

MD Anderson Cancer Center
Houston, Texas 77030

More Details

Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

Study Contact
844-434-4210
Participate-In-This-Study1@its.jnj.com