A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With HR+ Breast Cancer and Other Select Solid Tumors

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?

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 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

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)
* For non-breast cancer: prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway,
* Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 requiring antihyperglycemic medication
* Known active central nervous system (CNS) metastases.

Conditions6

Locations9 sites

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