Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced that a detailed analysis of the positive Phase III INAVO120 results, evaluating Itovebi^TM (inavolisib) in combination with palbociclib (Ibrance^®) and fulvestrant was published in the New England Journal of Medicine. The U.S. Food and Drug Administration (FDA) recently approved Itovebi in combination with palbociclib and fulvestrant, for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (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 are also being used for filing submissions to other global health authorities, including the European Medicines Agency.

“With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients,” said Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and one of the principal investigators of the INAVO120 study. “I’m confident this Itovebi-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis.”

Results showed the Itovebi-based regimen reduced the risk of disease worsening or death (progression-free survival [PFS]) 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<0.001). PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, which is characterized as difficult-to-treat disease. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.03 [boundary of 0.0098]). Follow-up for OS will continue to the next analysis.

“Publication of these Phase III results in the New England Journal of Medicine further highlights the transformative potential of the Itovebi-based regimen,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “This new treatment exemplifies our ambition to target specific disease pathways more effectively and improve outcomes in people with breast cancer, while also emphasizing the importance of comprehensive testing for mutations like PIK3CA at the time of diagnosis.”

The PIK3CA mutation is found in approximately 40% of HR-positive metastatic breast cancers and is associated with a poor prognosis. Historically, the use of PI3K targeted therapy in the first-line advanced setting has been limited and therefore testing for PIK3CA mutations is not common at the time of diagnosis. Early biomarker testing with an FDA-approved test, such as Foundation Medicine’s FoundationOne^®Liquid CDx, before first-line treatment is crucial to help identify people who may benefit from targeted therapy, such as Itovebi.

Itovebi 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 are exploring additional studies in breast cancer and other tumor types with the hope of bringing the benefit of this targeted therapy to more people with PIK3CA mutations and addressing patient unmet needs.