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 of TOS-358 in adults with select solid tumors who meet study enrollment criteria. The main questions it aims to answer are: 1. what is the maximum tolerated dose and recommended dose for phase 2? 2. how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?
• Locally advanced, recurrent, or metastatic, incurable (any number of previous lines of therapy is allowed), histologically or cytologically confirmed; HR +/HER2- breast cancer; squamous cell carcinoma of the head and neck; urothelial cancer; or endometrial cancer with no more than 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 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