INAVO122 (Inavolisib + Pertuzumab / Trastuzumab Maintenance)
Architecture
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A Phase III, double-blind randomized maintenance trial assessing inavolisib added to subcutaneous pertuzumab/trastuzumab following induction in HER2+ advanced breast cancer.
Location
Multinational
Category
Hudson Yards, New York
Year
2024
INAVO122 (NCT05894239) targets a specific subgroup: patients with HER2+ advanced breast cancer having concurrent PIK3CA mutations. After induction therapy with pertuzumab, trastuzumab, and a taxane, eligible participants are randomized to daily oral inavolisib versus placebo, each in combination with tri-weekly PH-FDC SC injections. This design reflects a deepening of precision medicine, aiming to maintain and deepen responses by targeting specific resistance pathways in patients who have already shown initial benefit.
Enrollment ramped up in early 2024, and by the end of Q1, approximately 15 patients had been randomized across sites in North America, Europe, and Asia. Interim analysis and futility thresholds are built into the protocol to ensure patient safety and trial efficiency. In addition to PFS and overall survival, secondary outcomes include duration of response, quality of life (utilizing validated instruments like EORTC QLQ-C30), and pharmacodynamic biomarkers of PI3K pathway activity in plasma ctDNA samples.
The biological rationale hinges on combating resistance: PI3K pathway activation is a documented escape mechanism following HER2-targeted induction. By combining targeted HER2 suppression with degradation of PI3Kα, the trial seeks to extend disease control without increasing toxicity significantly. Operationally, daily oral dosing aims to improve convenience and adherence in the maintenance setting, compared to continuous IV regimens.
Anticipated results are projected for late 2025. Should this regimen extend PFS and maintain safety, it may redefine maintenance strategies for HER2+ metastatic breast cancer. Favorable outcomes could lead to regulatory filings and encourage adoption within personalized therapy frameworks that focus on molecular tumor profiles beyond HER2.
