TOS-358, Totus Medicines’ covalent, pan-mutant, alpha-selective PI3Kα inhibitor, demonstrated encouraging early Phase 1b combination data with fulvestrant in heavily pre-treated HR+/HER2− metastatic breast cancer patients. Results presented at ESMO Breast Cancer 2026 showed a 100% disease control rate, durable responses beyond 24 weeks, and a differentiated safety profile designed to overcome key limitations of existing PI3Kα therapies.

Interim Phase 1a data for TOS-358 address key limitations of existing PI3Kα therapies through covalent target engagement, alpha selectivity, and broad activity across PI3Kα mutations. The presentation showcases early safety and efficacy findings in patients with PI3Kα-mutant solid tumors, including HR+/HER2− metastatic breast cancer.

This phase 1/1b study is open and enrolling patients with hormone-receptor positive (HR+) breast, endometrial or head & neck cancers that express PI3K-alpha mutations. Patients may be eligible for the study if they are 18 years or older, have good health status and life expectancy, no history of diabetes and no significant secondary cancers, heart conditions or other significant medical conditions (must meet all requirements for the study which will be assessed by the study doctor). TOS-358 is an oral medication taken twice daily. The purpose of the study is to evaluate the safety and tolerability of TOS-358 at different dose levels and to assess whether TOS-358 has any effect on tumors.