Phase III (INAVO120) results show that inavolisib in combination with palbociclib and fulvestrant significantly improved progression-free survival in the first-line setting
PIK3CA mutations, found in approximately 40% of HR-positive breast cancers, are linked to tumour growth, disease progression, and treatment resistance
Data will be shared with health authorities and presented at an upcoming medical meeting
Basel, 5 December 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive results from the Phase III INAVO120 study of the investigational therapy, inavolisib, in combination with palbociclib (Ibrance®) and fulvestrant as a potential first-line treatment option for people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful improvement compared to palbociclib and fulvestrant alone. Overall survival data were immature at this time, but a clear positive trend has been observed. Follow-up will continue to the next analysis.
"These pivotal study results for this inavolisib combination could represent a transformative medical advance for people with PIK3CA-mutated HR-positive breast cancer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We look forward to expanding our portfolio of breast cancer medicines into the HR-positive space and bringing this potentially best-in-class new treatment option to patients as quickly as possible."
The inavolisib combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, with no new safety signals observed.
Inavolisib is an oral therapy with high in vitro potency and selectivity for PI3Kα inhibition and the ability to specifically trigger the breakdown of mutant PI3Kα protein. With this unique dual mechanism of action, inavolisib may provide well-tolerated, durable disease control and potentially improved outcomes for people with HR-positive/HER2-negative, PIK3CA-mutated advanced breast cancer. PIK3CA mutations can lead to mutated PI3Kα protein which contributes to uncontrolled tumour growth, disease progression and resistance to endocrine-based treatment.
Inavolisib is currently being investigated in three Phase III clinical studies in people with PIK3CA-mutated metastatic breast cancer (INAVO120, INAVO121, INAVO122) in various combinations.
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, 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.
About inavolisib
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 hormone receptor (HR)-positive, PIK3CA-mutated breast cancer, a common yet often overlooked mutation found in approximately 40% of this population.1 Inavolisib has been designed to help minimise the overall toxicity of treatment and is differentiated from other PI3K inhibitors due to its high in vitro potency and specificity for the PI3K alpha (PI3Kα) isoform inhibition, together with its unique mechanism of action, that leads to specific degradation of mutant PI3K alpha.3,4
Inavolisib is currently being investigated in three Roche-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer:
in combination with palbociclib and fulvestrant vs. palbociclib and fulvestrant in first-line HR-positive HER2-negative breast cancer (INAVO120),
in combination with fulvestrant vs. alpelisib plus fulvestrant in HR-positive HER2-negative breast cancer post-CDK4/6 inhibitor and endocrine combination therapy (INAVO121),6 and
in combination with pertuzumab plus trastuzumab for subcutaneous injection (Phesgo®) vs. Phesgo as maintenance therapy in 1L HER2-positive breast cancer (INAVO122)
About hormone receptor-positive breast cancer
Hormone receptor (HR)-positive breast cancer is the most prevalent type of all breast cancers.8 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumour growth.9 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.10-12 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 for resistance to endocrine therapy and CDK4/6 inhibitors.
About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in HER2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including estrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.
About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.
Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).
The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan