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

NCT06150157 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 88549968MPN10012023-505584-36-00
• Study Type: interventional
• Target: 220
• Locations: 8 countries
• Sites: 31

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). 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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration 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

  Up to 2 years

• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate

  Up to 2 years

• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate

  Up to 2 years

• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)

  Up to 2 years

Study Arms (1)

Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)

EXPERIMENTAL

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; Drug: Ruxolitinib; Drug: Momelotinib

Interventions

JNJ-88549968 DRUG

JNJ-88549968 will be administered.

Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)

Ruxolitinib DRUG

For US sites: Ruxolitinib will be administered for participants with MF only.

Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)

Momelotinib DRUG

For US sites: Momelotinib will be administered for participants with MF only.

Dose Escalation (Part 1), Dose Expansion (Part 2) and Part 1b (US only), Part 2b (US only)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (31)

City of Hope

Duarte, California, 91010, United States

RECRUITING

UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Moffit Cancer center

Tampa, Florida, 33612, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sarah Cannon Cancer Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Hopital Saint Louis

Paris, 75475, France

RECRUITING

CH LYON SUD - Hematology

Pierre-Bénite, 69495, France

RECRUITING

Universitaetsklinikum der RWTH Aachen

Aachen, 52074, Germany

RECRUITING

Charite Campus Benjamin Franklin

Berlin, 12203, Germany

RECRUITING

Med. Universitatsklinik Essen

Essen, 45147, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

RECRUITING

Carmel Medical Center

Haifa, 3436212, Israel

RECRUITING

Hadassah University Hospita Ein Kerem

Jerusalem, 9112001, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 5266202, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

RECRUITING

Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

RECRUITING

Policlinico di Milano

Milan, 21022, Italy

RECRUITING

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

RECRUITING

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

RECRUITING

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG, United Kingdom

RECRUITING

Guy's and St Thomas' Hospital

London, SE1 9RT, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

ruxolitinib; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: November 29, 2023
• Study Start: December 20, 2023
• Primary Completion (Estimated): December 4, 2026
• Study Completion (Estimated): April 12, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); IT (2); DE (6); US (10); CA (2); IL (4); FR (2); GB (3)