A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults with Select Solid Tumors
Purpose
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?
Conditions
- Squamous Cell Carcinoma of Head and Neck
- Urothelial Carcinoma
- Endometrial Cancer
- HR+/HER2-negative Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- TOS-358 Single Agent Arm: Part 1(multiple ascending doses, QD or BID): locally advanced, recurrent or metastatic select solid tumors with PIK3CA mutation per local assessment; Part 2 (RP2D determined in Part 1) Patients with locally advanced, recurrent or metastatic select solid tumors with PIK3CA mutation per local assessment will be enrolled protocol defined groups
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental TOS-358 Single Agent Arm |
Multiple doses of TOS-358 for oral administration. |
|
Recruiting Locations
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Totus Medicines
Detailed 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. Adult subjects with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer, squamous cell carcinoma of the head and neck, urothelial cancer, or endometrial cancer with known PIK3CA mutations or amplifications (as determined at a College of American Pathologists/clinical laboratory improvement amendments [CAP/CLIA]-certified or equivalently accredited diagnostic laboratory using a validated test), who meet all of the eligibility criteria will be enrolled in the Phase 1 portion of the study. In the dose finding portion of the study, TOS-358 will be evaluated as a single-agent at multiple dose levels administered orally until disease progression, unacceptable toxicity, or until meeting any other reason for discontinuation as specified in the protocol.