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

Study Identifier:
88549968MPN1001
CT.gov Identifier:
NCT06150157
EudraCT Identifier:
202350558436
EU Trial (CTIS) Number:
2023-505584-36-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

Considering participating in a START clinical trial?

Get Started

Study 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.

The aim of this study was to describe the safety of JNJ-88549968 as monotherapy for essential thrombocytosis (ET) and myelofibrosis (MF), as well as in combination with Ruxolitinib for MF, and to determine the recommended phase II dose (RP2D) and optimal dosing regimen in Part 1 (dose escalation); and to describe the safety profile of JNJ-88549968 as monotherapy for ET and MF at RP2D, as well as in combination with Ruxolitinib for MF, in Part 2 (cohort extension).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Unspecified Cancer
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
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
  • Must be 18 years of age or older (or the legal Age of majority in the research area, whichever is greater) when signing the informed consent form.
  • According to the 2022 World Health Organization (WHO) criteria, patients diagnosed with essential thrombocythemia (ET) or myelofibrosis (MF) and meeting the risk criteria specified in the study protocol are eligible.
  • Positive calreticulin (CALR) driver mutation in ET or MF
  • Previously received treatment as specified in the study protocol
  • The combined use of the treatments specified in the study protocol has been discontinued.
  • Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
  • Pre-drug administration clinical hematology and clinical biochemistry laboratory test values must meet the parameters specified in the protocol.
  • Subjects who are known to be HIV positive are eligible to participate in the study if they meet all the criteria of the study protocol.
  • For subjects of fertility, a high-sensitivity serum (e.g., β-human chorionic gonadotropin [hCG]) pregnancy test result must be negative at screening and within 72 hours prior to the first dose of study treatment, and consent must be given to further serum or urine pregnancy tests during the study.
  • Participants of childbearing potential must use at least one highly effective method of contraception throughout the study period and for at least 90 days after the last dose of study treatment.
  • Subjects using oral contraceptives must use additional barrier contraception.
  • Participants must agree that they will not be pregnant, breastfeeding, or planning to become pregnant during the study period or within 90 days after the last dose of study treatment.
  • Participants must agree not to donate or freeze their gametes (i.e., eggs or sperm) for future assisted reproductive purposes during the study period and for six months after the last dose of study treatment. Participants should consider preserving their gametes before study treatment, as cancer treatment may impair fertility.
  • Subjects must use condoms during the study period and for at least 90 days after the last dose of study treatment when engaging in any activity that could result in ejaculation with another person. If a subject's partner is fertile, the subject must use a condom (with or without spermicide), and the partner must also use a highly effective method of contraception.
  • Participants must agree not to plan for pregnancy during the study period or for 3 months after the last dose of study treatment.
  • Informed consent (ICF) must be signed, indicating that the participant understands the purpose and required procedures of the study and is willing to participate.
  • Willing and able to comply with the lifestyle restrictions stipulated in this plan
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:
  • Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
  • 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
  • Known allergy, hypersensitivity or intolerance to excipients used in research treatments
  • Chemotherapy, cytoreductive therapy, targeted therapy, or immunotherapy shall be administered 5 half-lives or 2 weeks (whichever is shorter) prior to the first dose of the planned investigational treatment, except as otherwise specified in the protocol.
  • Previous CALR mutation-targeted therapy
  • Subjects were screened for concurrent or recently diagnosed or treated malignancies. Exceptions were made if the investigator and sponsor's medical monitor considered squamous cell carcinoma and basal cell carcinoma of the skin, cervical carcinoma in situ, and any malignant tumor that had been cured or had a very low risk of recurrence to have occurred within one year of the first dose of study treatment. Subjects who had been cured of another malignant disease and showed no signs of recurrence ≥3 years after the end of treatment were allowed to enroll in the study.
  • Previous solid organ transplant
  • Candidates must meet any of the following hematopoietic stem cell transplantation criteria: a) having received allogeneic stem cell transplantation within ≤6 months prior to the first dose of JNJ-88549968, or b) having evidence of graft-versus-host disease (GVHD) requiring immunosuppressant therapy.
  • Patients with active autoimmune diseases requiring systemic immunosuppressive therapy (e.g., chronic corticosteroids, Methotrexate, or Tacrolimus).
  • The toxicity of previous anticancer treatment has not yet returned to baseline levels, or hair loss, peripheral neuropathy, and vitiligo have not returned to grade 1 or below, or have not returned to grade ≤2.
  • A clinically significant history of cardiovascular disease within 6 months prior to the first dose.
  • Clinically significant lung function impairment, especially requiring supplemental oxygen to maintain adequate oxygenation.
  • Evidence of active viral (including chronic ebV), bacterial, or uncontrolled systemic fungal infection requiring systemic treatment within 14 days prior to the first dose of treatment was observed in the study.
  • Fever (temperature ≥38.0°C/100.4°F) occurred within 48 hours prior to the first dose of treatment in the study.
  • Those who have undergone trauma or major surgery (e.g., requiring general anesthesia) within 28 days prior to the first dose of the study treatment.
  • Any serious underlying medical or mental illness (e.g., alcohol or drug abuse), dementia, or altered mental status; or any issues that may impair a subject's ability to receive or tolerate planned treatment at the research center, understand informed consent, or that the investigator deems participation in this study contraindicated or likely to obscure the assessments or outcomes specified in the study protocol.
  • Prohibited drugs that cannot be discontinued, substituted, or temporarily interrupted during the study period
  • The patient received a live attenuated vaccine within 4 weeks prior to the first dose of the study treatment.
  • Weight < 40 kg at screening and/or at the first dose of study treatment
  • Active infectious hepatitis: Positive hepatitis B serological reaction, known hepatitis C infection or positive hepatitis C virus serological test (anti-HCV antibody), and other known clinically active infectious liver diseases.
  • History of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
  • History of pneumonia or interstitial lung disease
  • 20
  • :
  • twenty one Subjects without evidence of stable anticoagulation therapy were defined as those who had not received modified anticoagulation therapy for ≥4 weeks prior to the first dose of study treatment.

Clinical Study Information for Healthcare Providers

By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

View Study Information

Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Andrew Sochacki
Status
Will Be Recruiting
Condition(s) Treated at Site
Unspecified Cancer
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Will Be Recruiting
Condition(s) Treated at Site
Unspecified Cancer