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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06150157
• Other study ID #: 88549968MPN1001
• Secondary ID: 2023-505584-36-0
• Status: Recruiting
• Phase: Phase 1
• Start date: December 20, 2023
• Est. completion date: November 19, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 19, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Myelofibrosis
• Myeloproliferative Disorders
• Neoplasms
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• JNJ-88549968
JNJ-88549968 will be administered.

Locations

Country	Name	City	State
Canada	University Health Network UHN Princess Margaret Cancer Centre	Toronto	Ontario
France	Hopital Saint Louis	Paris
France	CH LYON SUD - Hematology	Pierre Benite Cedex
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. Clinico Univ. de Valencia	Valencia
United Kingdom	University College London Hospitals Nhs Foundation Trust	London
United Kingdom	Churchill Hospital	Oxford
United States	University of Michigan	Ann Arbor	Michigan
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Cancer Institute	Nashville	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants With Dose Limiting Toxicity (DLT)	Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.	Approximately up to 35 days after first dose of study treatment
Primary	Part 1 and 2: Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 2 years
Primary	Part 1 and 2: Number of Participants with Adverse Events (AEs) by Severity	An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.	Up to 2 years
Secondary	Part 1 and 2: Serum Concentration of JNJ-88549968	Serum samples will be analyzed to determine concentrations of JNJ-88549968.	Up to 2 years
Secondary	Part 1 and 2: Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968	Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported.	Up to 2 years
Secondary	Part 1 and 2: Overall Response Rate	ORR is defined as the percentage of participants who achieve partial response (PR) and complete response (CR) according to modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) criteria and modified European Leukemia Net (ELN) consensus report.	Up to 2 years
Secondary	Part 1 and 2: Complete Response (CR) Rate	CR rate is defined as the percentage of participants who achieve a best response of CR according to disease as defined in modified IWG-MRT criteria and modified ELN consensus report.	Up to 2 years
Secondary	Part 1 and 2: Time to Response (TTR)	TTR is defined for participants who achieved PR or CR as the time from the first dose of study treatment to first response of PR or CR according to modified IWG-MRT criteria and modified ELN consensus report.	Up to 2 years
Secondary	Part 1 and 2: Duration of Response (DOR)	DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression, as defined in modified IWG-MRT criteria and modified ELN consensus report, or death, whichever comes first.	Up to 2 years
Secondary	Part 2: Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden	Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure.	Baseline up to 2 years