A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults 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:what is the maximum tolerated dose and recommended dose for phase 2?how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?

Key Inclusion CriteriaLocally advanced, recurrent, or metastatic, incurable (any number of previous lines of therapy is allowed), histologically or cytologically confirmed: colorectal cancer; gastric cancer; non-small cell lung cancer; HER2- breast cancer; squamous cell carcinoma of the head and neck; urothelial cancer; or select gynecologic cancer (ovarian cancer, cervical cancer, or endometrial cancer)Willing and able to provide written informed consent for this studyAdults ≥ 18 years old at time of consentKnown PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory using a validated testMeasurable disease by RECIST 1.1Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Life expectancy ≥ 3 months, as determined by the investigatorAdequate bone marrow, liver, and kidney function within 14 days prior to first dose of investigational productFasting plasma glucose < 126 mg/dL AND hemoglobin A1c (HbA1c) < 5.7%Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory testKey Exclusion CriteriaRecent systemic anticancer treatment prior to start of treatmentPrior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway, except for patients with breast cancerSecond malignancy (solid or hematologic) within the past 3 years except: Adequately treated basal cell or squamous cell skin cancer; carcinoma in situ of the cervix, or prostate cancer with Gleason score < 6 and undetectable prostate specific antigen over 12 months ;ductal breast carcinoma in situ with full surgical resection (ie, negative margins); treated medullary or papillary thyroid cancer; metaplastic breast cancerHistory of diabetes of any typeBody mass index (BMI) ≥ 30Cushing syndromeCongestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to the first dose of investigational productKnown active central nervous system (CNS) metastases.