UPCC 09923 A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor, TOS-358, in Adult Subjects with Select Solid Tumors

Investigating the Safety and Tolerability of an Investigational Medication in Breast Cancer

Enrolling By Invitation
18 years or above
Female
Phase 1
241 participants needed
1 Location

Brief description of study

The goal of this clinical trial is to evaluate the safety and efficacy of TOS-358 in women with HR+ HER2- metastatic breast cancer whose tumors have a mutation in PIK3CA and who meet all other study enrollment criteria. The main questions it aims to answer are:

  1. Phase 1a: what is the maximum tolerated dose and recommended dose for phase 2?
  2. Phase 1a: how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?
  3. Phase 1b: how safe and effective is TOS-358 when given with standard of care medicines for HR+HER2- metastatic breast cancer (fulvestrant and CDK4/6i)

Detailed description of study

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.

Women with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer with known PIK3CA mutations or amplifications and who meet all of the eligibility criteria will be enrolled in 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. In the Phase 1b portion, TOS-358 will be combined with fulvestrant +/- CDK4/6i.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: HR+/HER2-negative Breast Cancer
  • Age: 18 years or above
  • Gender: Female

Key Inclusion Criteria

  • Locally advanced, recurrent, or metastatic HR +/HER2- breast cancer
  • Up to 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 or evaluable 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

  • Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2
  • Known active central nervous system (CNS) metastases
  • PTEN mutations

This study investigates the safety and tolerability of an investigational medication for women with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The study focuses on participants whose tumors have mutations in the PIK3CA gene. The purpose is to find the safest and most effective dose of the investigational medication when taken alone or with standard treatments like fulvestrant and CDK4/6 inhibitors.

Participants in the study will receive the investigational medication orally, either once or twice a day. Initially, the study will determine the maximum tolerated dose and the recommended dose for the next phase. Later, it will assess safety and tolerability in specific tumor groups. In the second part of the study, the investigational medication will be combined with other standard treatments for breast cancer.

  • Who can participate: Adults aged 18 and older with HR+ HER2- breast cancer, who have up to 3 prior treatments for metastatic disease, may be eligible. Participants must have PIK3CA mutations or amplifications and meet other health criteria.
  • Study details: Participants will take the investigational medication orally, either alone or with other standard breast cancer treatments. The study will assess the medication's safety and tolerability at different doses.
Updated on 28 Jul 2026. Study ID: 23-0453
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