Roche's inavolisib, an investigational oral therapy, has been granted Priority Review by the U.S. Food and Drug Administration (FDA) for the treatment of advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with a PIK3CA mutation. The drug, in combination with palbociclib and fulvestrant, is intended for patients whose cancer has recurred on or within 12 months of completing adjuvant endocrine treatment. This decision is based on the promising results from the Phase III INAVO120 trial, highlighting the potential of inavolisib to significantly improve outcomes for this patient population.
INAVO120 Trial Results
The INAVO120 study demonstrated that the inavolisib-based regimen more than doubled progression-free survival (PFS), reducing the risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001) in the first-line setting. While overall survival (OS) data were immature at the time of primary analysis, a positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338), with follow-up continuing for further analysis. These results suggest a substantial clinical benefit for patients with PIK3CA-mutated breast cancer.
Clinical Significance
Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, stated, “The addition of inavolisib to standard of care treatment significantly delayed disease progression in the first-line setting and has the potential to extend survival for people with metastatic breast cancers that harbour PIK3CA mutations.” The PIK3CA mutation is present in approximately 40% of HR-positive metastatic breast cancers, making early testing for this mutation crucial in identifying patients who may benefit from targeted therapy.
Inavolisib Mechanism and Design
Inavolisib is designed to minimize the overall burden and toxicity of treatment. It is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and its unique mechanism of action facilitates the degradation of mutated PI3K alpha.
Regulatory and Development Context
The FDA has set a Prescription Drug User Fee Act (PDUFA) date of November 27, 2024, for inavolisib. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency. Inavolisib has also been granted FDA Breakthrough Therapy Designation based on the INAVO120 trial. Roche is currently investigating inavolisib in three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations.
