inavolisib

Inavolisib is a small molecule inhibitor and degrader of mutant phosphatidylinositol 3-kinase alpha (PI3Kα), specifically targeting the PIK3CA gene mutation. It inhibits the enzymatic activity of PI3Kα, blocks phosphorylation of PIP2 to PIP3, thereby inhibiting downstream AKT signaling, reducing tumor cell proliferation and inducing apoptosis in PIK3CA-mutated breast cancer cells. In addition to inhibition, it promotes degradation of the mutant p110α protein via proteasome-mediated pathways. It is used primarily in combination with palbociclib and fulvestrant for treating adults with endocrine-resistant, hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer harboring PIK3CA mutations. The drug was developed to overcome limitations seen with earlier PI3K inhibitors by mitigating pathway reactivation through feedback mechanisms. It was approved by the FDA in October 2024 and Health Canada in February 2025 for this indication.

Brand names

Itovebi

Other names

inavolisib