Phase 1/1b RGT-490 mutant-selective PI3Kα inhibitor in PIK3CA-mutant solid tumors.

This first-in-human, open-label Phase 1/1b study tests RGT-490, an oral small molecule designed as a mutant-selective PI3Kα (PIK3CA) inhibitor, aiming to suppress oncogenic PI3K pathway signaling while potentially reducing toxicities driven by wild-type PI3Kα inhibition. The Phase 1 dose-escalation enrolls adults with unresectable locally advanced or metastatic PIK3CA-mutated solid tumors to define safety, tolerability, pharmacokinetics, and a recommended expansion dose; Phase 1b then expands in HR+/HER2- metastatic breast cancer with PIK3CA mutation after progression on prior therapy. Regor Pharmaceuticals sponsors the trial, positioning RGT-490 against a validated but tolerability-limited target class where hyperglycemia and rash have constrained earlier PI3Kα approaches. Clinically, patients in the breast cancer expansion typically receive sequential endocrine therapy plus targeted agents (CDK4/6 and PI3K/AKT pathway drugs when biomarker-eligible), then move to chemotherapy; this study explores whether a next-generation, mutation-selective PI3Kα approach can deliver single-agent activity with a more manageable safety profile.