This is a first-in-human, open-label, multi-center Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of PRT12396 in participants with high-risk polycythemia vera (PV) and myelofibrosis (MF), and to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE\[s\]). The study consists of a dose-escalation phase followed by a dose-expansion phase to further evaluate selected dose level(s).
Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures.
Confirmed diagnosis of PV or MF according to WHO 2016 or revised ICC/WHO 2022 criteria
Documented presence of a JAK2 V617 mutation
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
History of another malignancy within 3 years prior to enrollment, except for malignancy considered cured with low risk of recurrence.
Clinically significant anemia due to nutritional deficiency or hemolytic disorders.
Active or uncontrolled infection requiring systemic therapy or hospitalization.
Any other medical or psychiatric conditions that, in the Investigator's judgment, would increase risk or interfere with study participation or interpretation of results.