FDA grants priority review to Genentech’s Inavolisib

Genentech, a member of the Roche Group, announced that the USFDA has accepted the company’s new drug application and granted priority review to inavolisib, an investigational oral therapy, in combination with palbociclib (Ibrance) and fulvestrant. The inavolisib-based regimen was evaluated in adult patients with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.

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 per cent compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95 per cent CI: 0.32-0.59, p<0.0001) in the first-line setting. Overall survival (OS) data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95 per cent CI: 0.43-0.97, p=0.0338 [boundary of 0.0098]). 

The PIK3CA mutation is found in approximately 40 per cent 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 November 27, 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.

Genentech recently announced the inavolisib-based regimen has been granted FDA ‘Breakthrough Therapy’ designation based on INAVO120, the 29th for Genentech’s oncology portfolio. Additional analyses of INAVO120 will be presented in an oral abstract session at the 2024 American Society of Clinical Oncology annual meeting, taking place May 31 to June 4, 2024.

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. We continue to evaluate potential clinical development program expansion opportunities to address patient unmet needs in various tumour types across oncology.

About the INAVO120 study

The INAVO120 study [NCT04191499] is a Phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

Beyond INAVO120, inavolisib is currently being investigated in two additional company-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:

• in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 inhibitor and endocrine combination therapy (INAVO121; NCT05646862), and
• in combination with dual HER2 blockade versus dual HER2 blockade and optional physician’s choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).