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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 HBV/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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1a Dose Escalation Cohort Disease Group A - with MF 		INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
Experimental
Part 1a Dose Escalation Cohort Disease Group A - with ET 		INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with essential thrombocythemia (ET) will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
Experimental
Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R 		INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
  • Drug: Ruxolitinib
    Rux will be administered according to Prescribing Information/SmPC.
    Other names:
    • Jakafi
Experimental
Part 1b: Dose Expansion - with MF 		INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
Experimental
Part 1b: Dose Expansion - with TGB-MF SubOpt R 		INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
  • Drug: Ruxolitinib
    Rux will be administered according to Prescribing Information/SmPC.
    Other names:
    • Jakafi
Experimental
Part 1b: Dose Expansion - with ET 		INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
Experimental
Part 1c: Dose Expansion 		INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.
  • Drug: INCA033989
    INCA033989 will be administered at protocol defined dose.
  • Drug: Ruxolitinib
    Rux will be administered according to Prescribing Information/SmPC.
    Other names:
    • Jakafi

Recruiting Locations

The University of Kansas Cancer Center
Westwood, Kansas 66205

More Details

Status
Recruiting
Sponsor
Incyte Corporation

Study Contact

Incyte Corporation Call Center (US)
1.855.463.3463
medinfo@incyte.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.