PI3Kα Inhibitor and Degrader Inavolisib Can Co-opt FGFR2 to Enhance Responses in Patients with PIK3CA-Mutated Solid Tumors and in Preclinical Models.

ABSTRACT:

Purpose

PIK3CA mutations frequently drive solid tumors, particularly hormone receptor-positive breast cancer. Inavolisib, an ATP-competitive p110α inhibitor, also promotes the degradation of mutated p110α. PI3K inhibitors have generally shown modest single-agent activity and have safety concerns.

Patients and methods

A first-in-human phase 1 study (NCT03006172) evaluated oral inavolisib in patients with PIK3CA-mutated solid tumors to determine the maximum tolerated dose and safety. Correlative analyses included ctDNA. Preclinical studies in cell lines and xenografts elucidated the role of FGFR2.

Results

The maximum tolerated dose was 9 mg daily, with a manageable safety profile (e.g., hyperglycemia and diarrhea). Inavolisib showed linear pharmacokinetics, consistent p

SUBMITTER: Juric D 

PROVIDER: S-EPMC12770939 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature