Brief Title: TOS-358 in Adults With Select Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Determine the rate of dose-limiting toxicities (DLTs)

Primary Outcome 1 - Timeframe: First 21 days of treatment

Primary Outcome 2 - Measure: Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5

Primary Outcome 2 - Timeframe: Start of treatment to 30 days after last dose

CONDITION

• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma
• Endometrial Cancer
• HR+/HER2-negative Breast Cancer

ELIGIBILITY

Key Inclusion Criteria
* 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

- * 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 ≥ 3 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 < 126 mg/dL AND hemoglobin A1c (HbA1c) < 6.5% - * Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory test
Key Exclusion Criteria
* Recent systemic anticancer treatment prior to start of treatment (EXCEPTION: Patients with breast cancer who were receiving a fulvestrant-containing regimen at the time of informed consent may remain on fulvestrant while receiving study treatment)

- * Prior 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 cancer

- * Second 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 cancer - * History of diabetes of any type - * Cushing syndrome - * Congestive 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 product - * Known active central nervous system (CNS) metastases.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Glenn Michelson, MD

Role: Study Director

Affiliation: Totus Medicines

Overall Contact

Name: Clinical Trials

Phone: Please e-mail

Email: [email protected]

LOCATION