A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-Alpha Inhibitor, TOS-358, in Adult Subjects With Select Solid Tumors
Totus Medicines
Summary
The goal of this clinical trial is to evaluate the safety and efficacy of TOS-358 in women with HR+ HER2- metastatic breast cancer whose tumors have a mutation in PIK3CA and who meet all other study enrollment criteria. The main questions it aims to answer are: 1. Phase 1a: what is the maximum tolerated dose and recommended dose for phase 2? 2. Phase 1a: how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day? 3. Phase 1b: how safe and effective is TOS-358 when given with standard of care medicines for HR+HER2- metastatic breast cancer (fulvestrant and CDK4/6i)
Description
This study will be conducted in two parts: a dose finding portion to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of TOS-358 administered orally on once a day (QD) and twice daily (BID) schedules, and a dose expansion portion to evaluate safety and tolerability in tumor-specific cohorts administered TOS-358 at the recommended phase 2 dose and schedule. Women with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer with known PIK3CA mutations or amplifications and who meet all…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Key Inclusion Criteria * Locally advanced, recurrent, or metastatic HR +/HER2- breast cancer * Up to 3 prior lines of therapy for metastatic disease * Willing and able to provide written informed consent for this study * Adults ≥ 18 years old at time of consent * Known PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory using a validated test * Measurable or evaluable disease by RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy ≥ 6 months, as determined by the investigator…
Interventions
- DrugTOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor
- DrugFulvestrant
Intramuscular SERD at standard doses
- DrugPalbociclib
CDK4/6 inhibitor at standard doses
- DrugRibociclib
CDK4/6 inhibitor at standard doses
Locations (18)
- Northwestern Memorial HospitalChicago, Illinois
- Beth Israel Deaconess Medical CenterBoston, Massachusetts
- Dana-Farber Cancer InstituteBoston, Massachusetts
- Comprehensive Cancer Centers of NevadaLas Vegas, Nevada
- University of PennsylvaniaPhiladelphia, Pennsylvania
- Sarah Cannon Cancer CenterNashville, Tennessee