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

NCT06034002
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
290
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Lead sponsor
Incyte Corporation
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Start date
2023-12-04
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Number of sites
13
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Summary
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.
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Short title
A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
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Official title
A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-10-29
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First posted
2023-09-13
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Registry last updated
2026-04-17
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Primary completion date
2028-10-29
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Start date
2023-12-04
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Participants
290
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Participant count basis
Estimated
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Planned participants
290
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Protocol amendments
5
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Number of sites
13
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Registry sponsor category
Industry
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Lead sponsor
Incyte Corporation
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06034002
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ClinicalTrials.gov ID
NCT06034002
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Number of participants with Dose Limiting Toxicities (DLTs)

    Timeframe: 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)

    Timeframe: 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.

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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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

    Timeframe: Week 12 and Week 24

    Mean change in TSS from baseline.

  8. Mean change in disease-related allele burden

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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.

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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.

Sources for eligibility
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  • City of Hope Medical CenterDuarte, United StatesRecruiting
  • Stanford Cancer InstitutePalo Alto, United StatesRecruiting
  • University of Miami Health SystemMiami, United StatesRecruiting
  • The University of Kansas Cancer CenterWestwood, United StatesRecruiting
  • Johns Hopkins HospitalBaltimore, United StatesRecruiting
  • Dana Farber Cancer InstituteBoston, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • Icahn School of Medicine At Mount SinaiNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Wake Forest Baptist Medical CenterWinston-Salem, United StatesRecruiting
  • Cleveland ClinicCleveland, United StatesRecruiting
  • Vanderbilt University Medical CenterNashville, United StatesRecruiting
  • Md Anderson Cancer CenterHouston, United StatesRecruiting
Sources for sites
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Sources for references
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Related records

Drugs (1)

Lead sponsors (1)

Conditions (4)

Targets (2)