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

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: Recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: JNJ-88549968; Drug: Ruxolitinib; Drug: Momelotinib

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

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
  • 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
• 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
• 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
  • 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
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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. 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

Outcome Measure	Measure Description	Time Frame
Part 1, Part 1b (US Only): 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. 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)	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	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

Outcome Measure	Measure Description	Time Frame
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968	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	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	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	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)	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)	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	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

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): December 4, 2026
• Study Completion (Estimated): May 12, 2028

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Hemic and Lymphatic Diseases; Thrombocytosis; Neoplasms; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; ruxolitinib
• Other Study ID Numbers: 88549968MPN1001 (Janssen Research & Development, LLC); 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