UPCC 51423 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

Investigational Study on CALR-Mutated Blood Cancers

Enrolling By Invitation
18 years or above
All
Phase 1
241 participants needed
1 Location

Brief description of study

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 of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Neoplasms
  • Age: 18 years or above
  • Gender: All

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

This study investigates the safety and effectiveness of an investigational medication for individuals with CALR-mutated myeloproliferative neoplasms, which include conditions like essential thrombocythemia (ET) and myelofibrosis (MF). The purpose of this study is to find the best dose and schedule for the investigational medication.

Participants will receive the investigational medication either alone or in combination with other treatments like ruxolitinib or momelotinib for MF. The study will monitor the participants for any side effects and measure how the medication affects their condition. The study includes different parts to explore how safe the investigational medication is and what dosage works best.

  • Who can participate: Participants must be 18 years or older with a CALR mutation associated with essential thrombocythemia or myelofibrosis, have a performance status grade of 2 or lower, and may be eligible for ruxolitinib therapy if they are naive to JAK inhibitors.
  • Study details: Participants will take the investigational medication, either alone or with other treatments, and will be monitored for safety and dosage effects. The study aims to find the best dosing schedule for the investigational medication.
Updated on 31 Jul 2026. Study ID: 24-0112
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