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

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).

Eligibility

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 0-2
* 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.

Conditions7

Interventions1

Locations8 sites

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