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

September 4, 2026 updated by: Janssen Research & Development, LLC

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

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 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1Z5
        • Recruiting
        • Princess Margaret Cancer Centre University Health Network
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Jewish General Hospital
  • China
      • Beijing, China, 100032
        • Recruiting
        • Peking Union Medical College Hospital
      • Tianjin, China, 301617
        • Recruiting
        • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
  • France
      • Paris, France, 75475
        • Recruiting
        • Hopital Saint Louis
      • Pierre-Bénite, France, 69495
        • Recruiting
        • CH LYON SUD - Hematology
      • Toulouse, France, 31059
        • Recruiting
        • Institut Universitaire du Cancer Toulouse Oncopole
  • Germany
      • Aachen, Germany, 52074
        • Recruiting
        • Universitaetsklinikum der RWTH Aachen
      • Berlin, Germany, 12203
        • Recruiting
        • Charite Campus Benjamin Franklin
      • Essen, Germany, 45147
        • Recruiting
        • Med. Universitatsklinik Essen
      • Hanover, Germany, 30625
        • Recruiting
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitaetsklinikum Heidelberg
      • Regensburg, Germany, 93053
        • Recruiting
        • Universitaetsklinikum Regensburg
  • Israel
      • Haifa, Israel, 3436212
        • Recruiting
        • Carmel Medical Center
      • Jerusalem, Israel, 9112001
        • Recruiting
        • Hadassah University Hospita Ein Kerem
      • Ramat Gan, Israel, 5266202
        • Recruiting
        • Sheba medical center
      • Tel Aviv, Israel, 64239
        • Recruiting
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Policlinico Sant'Orsola Malpighi
      • Milan, Italy, 21022
        • Recruiting
        • Policlinico di Milano
  • Japan
      • Bunkyō City, Japan, 113 8431
        • Recruiting
        • Juntendo University Hospital
      • Kashiwa, Japan, 277 8577
        • Recruiting
        • National Cancer Center Hospital East
  • Spain
      • Badalona, Spain, 08916
        • Recruiting
        • Hosp. Univ. Germans Trias I Pujol
      • Valencia, Spain, 46010
        • Recruiting
        • Hosp. Clinico Univ. de Valencia
  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • Recruiting
        • University College London Hospitals NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's and St Thomas' Hospital
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Churchill Hospital
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffit Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START MidWest
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Recruiting
        • START New Jersey
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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. Additional Cohorts may be added to assess different formulation or delivery methods. 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: Approximately up to 35 days after first dose of study treatment
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. For US only: A DLT is any adverse event attributed to study treatment that meets the criteria for severity and duration and that occurs during the evaluation periods unless it can be incontrovertibly attributed to disease or other extraneous cause such as an accident.
Approximately up to 35 days after first dose of study treatment
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
Time Frame: Up to 2 years
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
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
Time Frame: Up to 2 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
Time Frame: Up to 2 years
Serum samples will be analyzed to determine concentrations of JNJ-88549968.
Up to 2 years
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
Time Frame: Up to 2 years
Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported.
Up to 2 years
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
Time Frame: Up to 2 years
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
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
Time Frame: Up to 2 years
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
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
Time Frame: Up to 2 years
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
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
Time Frame: Up to 2 years
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
Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
Time Frame: Baseline up to 2 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 20, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 4, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 14, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 88549968MPN1001 (Janssen Research & Development, LLC)
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2023-505584-36-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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