Overview
This first-in-human, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722, an oral KAT6A protein degrader, in adults with locally advanced or metastatic Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. PRT13722 will be evaluated as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion (RDE) and evaluate preliminary clinical activity.
Description
This is a first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of PRT13722, a selective oral KAT6A protein degrader, in adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer. The study will evaluate the safety, tolerability, dose-limiting toxicities, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722 administered as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion and evaluate preliminary clinical activity.
The study is conducted in three parts:
Part 1: Monotherapy dose escalation and backfill cohorts. Part 2: Combination dose-escalation cohorts with fulvestrant, abemaciclib plus fulvestrant, and imlunestrant.
Part 3: Combination dose-expansion cohorts to further evaluate safety and preliminary efficacy at the selected dose levels.
Up to approximately 240 participants are planned for enrollment across the three parts of the study.
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.
- histological or cytological diagnosis of locally advanced or metastatic HR-positive/HER2-negative breast cancer
- Disease progression following prior standard therapy and eligible for the assigned study cohort
- Measurable or evaluable disease per RECIST v1.1
- Willingness to provide tumor tissue for biomarker analyses
- Eastern Cooperative Oncology Group performance status of 0-1
- Negative serum or urine pregnancy test and agree to use highly effective contraception or maintain true abstinence.
- Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)
Exclusion Criteria:
- Untreated, symptomatic, or unstable brain metastases
- Symptomatic visceral disease at risk of imminent life-threatening complications
- Uncontrolled infection or significant concurrent medical conditions
- Clinically significant cardiovascular disease or prolonged QT syndrome
- Pregnancy or breastfeeding
- Prior treatment with a KAT6-targeting agent
- Recent anticancer therapy, radiotherapy, or major surgery
- Use of prohibited concomitant medications, including strong CYP3A4 inhibitors or inducers, proton pump inhibitors, P-gp inhibitors or inducers, and breast cancer resistance protein inhibitors
- Participation in another interventional clinical study
- Any condition that would interfere with study participation or evaluation of study results
