A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms

About

Brief Summary

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).

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

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 0-1
Estimate life expectancy of ≥12 weeks per investigator assessment.
Negative serum or urine pregnancy test and agree to use contraception or maintain true abstinence.
Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)

Exclusion Criteria:

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.
Clinically significant or uncontrolled medical conditions, including active infection or cardiovascular disease, that would increase risk or interfere with study participation.
Unresolved toxicity Grade >1 from prior anticancer therapy, except for alopecia or peripheral neuropathy Grade ≤2.
Pregnancy or breastfeeding
Known sensitivity or contraindication to any component of study, or the excipients of study treatment.
Prior systemic therapy for PV or MF, prior or planned allogeneic hematopoietic stem-cell transplantation, recent major surgery, prior splenectomy or prior splenic irradiation, or use of hematopoietic growth factors within protocol-defined washout periods.
Use of strong or moderate cytochrome P450 (CYP) 3A4 inhibitor or inducer, sensitive CYP3A substrates with narrow therapeutic range, or acid-reducing agents that cannot be discontinued prior to study treatment.
Participation in another interventional clinical study.