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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
225
INCA033989 will be administered at protocol defined dose.
Rux will be administered according to Prescribing Information/SmPC.
Number of participants with Dose Limiting Toxicities (DLTs)
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Time frame: Up to 28 days
Number of participants with Treatment-emergent Adverse Events (TEAEs)
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
Time frame: Up to 3 years and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation
Number of participants with TEAEs leading to dose modification or discontinuation.
Time frame: Up to 3 years and 60 days
Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
Time frame: Up to 3 years and 60 days
Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
Time frame: Up to 3 years and 60 days
Participants with MF with symptomatic anemia: Anemia Response
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.
Time frame: Up to 3 years and 60 days
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Royal Brisbane and Women'S Hospital
Herston, Queensland, Australia
RECRUITINGRoyal Adelaide Hospital
Adelaide, South Australia, Australia
RECRUITINGPeter Maccallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGThe Alfred Hospital
Melbourne, Victoria, Australia
RECRUITINGPrincess Margaret Cancer Center
Toronto, Ontario, Canada
RECRUITINGHopital Maisonneuve-Rosemont, Montreal, Qc
Montreal, Quebec, Canada
RECRUITINGOdense University Hospital
Odense C, Denmark
WITHDRAWNSjaellands Universitetshospital
Roskilde, Denmark
RECRUITINGVejle Hospital
Vejle, Denmark
RECRUITINGInstitut Bergonie
Bordeaux, France
RECRUITING...and 19 more locations
Participants With ET: Response Rate
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Time frame: Up to 3 years and 60 days
Participants With ET: Mean change from baseline of total symptom score (TSS)
Mean change of TSS from baseline.
Time frame: Up to 3 years and 60 days
Mean change in disease-related allele burden
Mean change in disease-related allele burden.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmax of INCA33989
Defined as maximum observed plasma concentration of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Tmax of INCA033989
Defined as the time to reach the maximum plasma concentration of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmin of INCA33989
Defined as the minimum observed plasma concentration of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC(0-t) of INCA33989
Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: CL/F of INCA33989
Defined as the apparent oral dose clearance of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Vz/F of INCA33989
Defined as the apparent oral dose volume of distribution of INCA33989.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: t1/2 of INCA33989
Defined as the apparent terminal phase disposition half-life of INCA33989.
Time frame: Up to 3 years and 60 days