Roche has announced positive topline results from the overall survival (OS) analysis of the phase III INAVO120 study, which investigated Itovebi (inavolisib) in combination with palbociclib and fulvestrant for patients with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The study met its key secondary endpoint, demonstrating a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen compared to palbociclib and fulvestrant alone. These findings suggest a potential new standard of care for this patient population. The full OS results from the phase III INAVO120 study will be presented at an upcoming medical meeting.
Clinical Significance of INAVO120 Results
The INAVO120 study is a phase III, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of Itovebi (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.
Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, stated, "The INAVO120 overall survival results show that the Itovebi-based regimen not only delayed disease progression, but also helped people with advanced HR-positive, PIK3CA-mutated breast cancer live longer. These findings underscore our ambition to improve survival rates for people with breast cancer. The Itovebi-based regimen has the potential to become the new standard of care for these patients."
The OS results build upon the previously reported primary analysis, which showed that the Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.001) in the first-line setting. OS data were immature at the time of primary analysis, but a clear positive trend was observed at that time (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)). No new safety signals were observed since the previous analysis.
Regulatory and Development Landscape
The US Food and Drug Administration (FDA) approved the Itovebi-based regimen in October 2024 for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Data from INAVO120, recently published in the New England Journal of Medicine, are also being reviewed by other global health authorities, including the European Medicines Agency.
Itovebi is currently being investigated in four company-sponsored phase III clinical studies (INAVO120, INAVO121, INAVO122, INAVO123) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. Roche is exploring additional studies in breast cancer and other tumour types with the hope of bringing the benefit of this targeted therapy to more people with PIK3CA-mutated cancer and addressing patient unmet needs.
About Itovebi (inavolisib)
Itovebi is an 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 (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, who often have a poor prognosis and are in urgent need of new treatment options. Itovebi 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.
Breast Cancer Context
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.
