Clinical trial NCT06150157: A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Myeloproliferative Disorders
Essential Thrombocythemia
Neoplasms
Myelofibrosis
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2023-11-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).


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

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

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Approximately up to 35 days after first dose of study treatment
measure: Part 1 and 2: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 2 years
measure: Part 1 and 2: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 2 years
Secondary outcomes:
measure: Part 1 and 2: Serum Concentration of JNJ-88549968
timeFrame: Up to 2 years
measure: Part 1 and 2: Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
timeFrame: Up to 2 years
measure: Part 1 and 2: Overall Response Rate
timeFrame: Up to 2 years
measure: Part 1 and 2: Complete Response (CR) Rate
timeFrame: Up to 2 years
measure: Part 1 and 2: Time to Response (TTR)
timeFrame: Up to 2 years
measure: Part 1 and 2: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Part 2: Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
timeFrame: Baseline up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: Moffit Cancer center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Cancer Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre Benite Cedex
country: France
facility: CH LYON SUD - Hematology
city: Aachen
country: Germany
facility: Universitaetsklinikum der RWTH Aachen
city: Berlin
country: Germany
facility: Charite Campus Benjamin Franklin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: