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
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)
• 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
• Adequate bone marrow, liver, and kidney function within 14 days prior to first dose of investigational product
• Fasting plasma glucose \<= 140 mg/dL AND hemoglobin A1c (HbA1c) \<= 7.0%
• Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory test