Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06034002

A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a Monotherapy or in Combination With Ruxolitinib in participants with myeloproliferative neoplasms.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Myeloproliferative Neoplasms Blood Coagulation Disorders Blood Platelet Disorders Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Myeloproliferative Disorders Primary Myelofibrosis Thrombocythemia, Essential Thrombocytosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

City of Hope Medical Center, Duarte, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Life expectancy > 6 months.
  • Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
  • Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
  • Participants with MF or ET as defined in the protocol.

Exclusion criteria

  • Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
  • Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
  • Participants with laboratory values exceeding the protocol defined thresholds.
  • Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
  • Active invasive malignancy over the previous 2 years.
  • History of clinically significant or uncontrolled cardiac disease.
  • Active or chronic HBV or active HCV or known history of HIV.
  • Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
  • Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Treatment and study plan

INCA033989

Drug

INCA033989 will be administered at protocol defined dose.

Ruxolitinib

Drug

Rux will be administered according to Prescribing Information/SmPC.

Other names: Jakafi

Primary outcomes

  1. Number of participants with Dose Limiting Toxicities (DLTs)

    Time frame: Up to 28 days

    Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.

  2. Number of participants with Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to 3 years and 60 days

    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug, including those leading to dose modification or discontinuation.

Secondary outcomes

  1. Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF

    Time frame: Up to 3 years and 60 days

    Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

  2. Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol

    Time frame: Up to 24 weeks

    Defined as percentage of participants with a protocol defined Spleen Volume Reduction.

  3. Participants with symptomatic anemia: Anemia Response as defined in the protocol

    Time frame: Up to 24 weeks

    Anemia Response as defined by the protocol.

  4. Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET

    Time frame: Up to 3 years and 60 days

    Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

  5. Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation

    Time frame: Up to 3 years and 60 days

    To evaluate the safety of INCA033989.

  6. Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS)

    Time frame: Week 12 and Week 24

    Defined as the percentage of participants achieving ≥ 50% reduction from baseline in TSS.

  7. Mean change from baseline in TSS

    Time frame: Week 12 and Week 24

    Mean change in TSS from baseline.

  8. Mean change in disease-related allele burden

    Time frame: Up to 3 years and 60 days

    Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.

  9. Pharmacokinetics Parameter: Cmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as maximum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  10. Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the time to reach the maximum plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  11. Pharmacokinetics Parameter: Cmin of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the minimum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  12. Pharmacokinetics Parameter: AUC(0-t) of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the area under the concentration-time curve up to the last measurable concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  13. Pharmacokinetics Parameter: AUC 0-∞ of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the area under the concentration-time curve from 0 to infinity of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  14. Pharmacokinetics Parameter: CL/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the apparent oral dose clearance of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  15. Pharmacokinetics Parameter: Vz/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the apparent oral dose volume of distribution of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

  16. Pharmacokinetics Parameter: t1/2 of INCA033989 alone or for the combination of INCA033989 with ruxolitinib

    Time frame: Up to 3 years and 60 days

    Defined as the apparent terminal phase disposition half-life of INCA033989 alone or for the combination of INCA033989 with ruxolitinib.

Study contacts

Contact information is provided by the study sponsor or research team.

Incyte Corporation Call Center (US)

CONTACT

[email protected]

1.855.463.3463

Incyte Corporation Call Center (ex-US)

CONTACT

[email protected]

+800 00027423

Sponsors and collaborators

Lead sponsor

Incyte Corporation

Industry

Registry information

Official study title

A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Sep 13, 2023
Registry last updated
Apr 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.