Roche Inavolisib gets USFDA priority review for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation

The Priority Review is based on the positive Phase III INAVO120 results, which showed the inavolisib-based regimen more than doubled progression-free survival, 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.3 Overall survival (OS) data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)). Follow-up for OS is continuing to the next analysis.

“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,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We welcome the FDA’s Priority Review designation for inavolisib, which underscores the urgency to bring this potential best-in-class treatment option to patients as quickly as possible.”

The PIK3CA mutation is found in approximately 40% of HR-positive metastatic breast cancers. Early testing for mutations like PIK3CA prior to initiating first-line treatment can help identify people who may benefit from targeted therapy.

Based on the Priority Review designation, the FDA has set a Prescription Drug User Fee Act date of 27 November, 2024. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

Roche recently announced the inavolisib-based regimen has been granted FDA Breakthrough Therapy Designation based on INAVO120, the 29th for Roche’s oncology portfolio. Additional analyses from INAVO120 will be presented in an oral abstract session at the 2024 American Society of Clinical Oncology Annual Meeting, taking place 31 May - 04 June.

Inavolisib is currently being investigated in three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. 

Inavolisib is an investigational, oral targeted treatment with best-in-class potential that could provide well-tolerated, durable disease control and potentially improved outcomes for people with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer, who often have a poor prognosis and are in urgent need of new treatment options. Inavolisib has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.

HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – oestrogen or progesterone – which can contribute to tumour growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

Read also: Head of Roche Pharma Partnering James Sabry to retire