Positive Results for Breast Cancer Study

The study met its key secondary endpoint, showing a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen compared with palbociclib and fulvestrant alone.

"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,” said Levi Garraway,  Roche’s Chief Medical Officer and Head of Global Product Development. “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.”

These 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. The full results from the OS analysis will be presented at an upcoming medical meeting.

The 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. We are 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.

The INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study 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.

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, Itovebi is currently being investigated in three additional company-sponsored phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:

• i. in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and endocrine combination therapy (INAVO121; NCT05646862).
• ii. in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
• iii. in combination with CDK4/6i and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in endocrine-sensitive, PIK3CA-mutated HR-positive/HER2-negative breast cancer (INAVO123; NCT06790693).
• See  Citation- Turner NC, Im SA, Saura C et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med 2024;391:1584 DOI: 10.1056/NEJMoa2404625.