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
160
INCA033989 will be administered at protocol defined dose.
Rux will be administered according to Prescribing Information/SmPC.
Royal Brisbane and Women'S Hospital
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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Herston, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Hopital Maisonneuve-Rosemont, Montreal, Qc
Montreal, Quebec, Canada
Sjaellands Universitetshospital
Roskilde, Denmark
Vejle Hospital
Vejle, Denmark
Institut Bergonie
Bordeaux, France
Chu Nimes
Nîmes, France
...and 18 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