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NCT Number: NCT05936359

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, and 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

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Royal Brisbane and Women'S Hospital, Herston, Queensland, Australia

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 and ET as defined in the protocol.

Exclusion criteria

  • Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
  • Active invasive malignancy over the previous 2 years.
  • Active HBV/HCV, HIV.
  • History of clinically significant or uncontrolled cardiac disease.
  • Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
  • Laboratory values outside the Protocol-defined ranges.
  • 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.
  • Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
  • 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 within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
  • For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

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 monotherapy and in combination with ruxolitinib

  3. Number of participants with TEAEs leading to dose modification or discontinuation

    Time frame: Up to 3 years and 60 days

    Number of participants with TEAEs 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 3 years and 60 days

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

  3. Participants with MF with symptomatic anemia: Anemia Response

    Time frame: Up to 3 years and 60 days

    For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.

  4. Participants With ET: Response Rate

    Time frame: Up to 3 years and 60 days

    Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.

  5. Participants With ET: Mean change from baseline of total symptom score (TSS)

    Time frame: Up to 3 years and 60 days

    Mean change of TSS from baseline.

  6. Mean change in disease-related allele burden

    Time frame: Up to 3 years and 60 days

    Mean change in disease-related allele burden.

  7. Pharmacokinetics Parameter: Cmax of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as maximum observed plasma concentration of INCA33989.

  8. Pharmacokinetics Parameter: Tmax of INCA033989

    Time frame: Up to 3 years and 60 days

    Defined as the time to reach the maximum plasma concentration of INCA33989.

  9. Pharmacokinetics Parameter: Cmin of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as the minimum observed plasma concentration of INCA33989.

  10. Pharmacokinetics Parameter: AUC(0-t) of INCA33989

    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 INCA33989.

  11. Pharmacokinetics Parameter: AUC 0-∞ of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.

  12. Pharmacokinetics Parameter: CL/F of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as the apparent oral dose clearance of INCA33989.

  13. Pharmacokinetics Parameter: Vz/F of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as the apparent oral dose volume of distribution of INCA33989.

  14. Pharmacokinetics Parameter: t1/2 of INCA33989

    Time frame: Up to 3 years and 60 days

    Defined as the apparent terminal phase disposition half-life of INCA33989.

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
Jul 7, 2023
Registry last updated
Mar 24, 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.

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