A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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?

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Totus Medicines

Criteria

Key Inclusion Criteria

• Locally 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 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) < 5.7%

• 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

• 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

• Body mass index (BMI) ≥ 30

• 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.