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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
230
INCA033989 will be administered at protocol defined dose.
Rux will be administered according to Prescribing Information/SmPC.
City of Hope Medical Center
Duarte, California, United States
RECRUITINGStanford Cancer Institute
Palo Alto, California, United States
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, including those 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 24 weeks
Participants with symptomatic anemia: Anemia Response as defined in the protocol
Anemia Response as defined by the protocol.
Time frame: Up to 24 weeks
Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET
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
Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of Miami Health System
Miami, Florida, United States
RECRUITINGThe University of Kansas Cancer Center
Westwood, Kansas, United States
RECRUITINGJohns Hopkins Hospital
Baltimore, Maryland, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGIcahn School of Medicine At Mount Sinai
New York, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGWake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
RECRUITING...and 3 more locations
To evaluate the safety of INCA033989.
Time frame: Up to 3 years and 60 days
Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS)
Defined as the percentage of participants achieving ≥ 50% reduction from baseline in TSS.
Time frame: Week 12 and Week 24
Mean change from baseline in TSS
Mean change in TSS from baseline.
Time frame: Week 12 and Week 24
Mean change in disease-related allele burden
Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmax of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as maximum observed plasma concentration of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the time to reach the maximum plasma concentration of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Cmin of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the minimum observed plasma concentration of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC(0-t) of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the area under the concentration-time curve from 0 to infinity of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: CL/F of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the apparent oral dose clearance of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: Vz/F of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the apparent oral dose volume of distribution of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days
Pharmacokinetics Parameter: t1/2 of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
Defined as the apparent terminal phase disposition half-life of INCA33989 alone or for the combination of INCA033989 with ruxolitinib.
Time frame: Up to 3 years and 60 days