FDA approves Roche’s Itovebi, a targeted treatment for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation

Roche announced that the United States Food and Drug Administration (FDA) approved Itovebi (inavolisib), in combination with palbociclib (Ibrance) 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. The PIK3CA mutation is found in approximately 40% of HR-positive metastatic breast cancers.

“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target,” 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. “The Itovebi-based regimen more than doubled progression-free survival and maintained a manageable safety and tolerability profile, adding a new standard in how PIK3CA-mutated breast cancers are treated.”

“With the approval of this Itovebi-based regimen, we continue our long-standing track record of cancer therapeutic discovery by offering an important new first-line option for people living with HR-positive breast cancer with a PIK3CA mutation,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Despite the high prevalence of PIK3CA mutations in this setting, treatment options have thus far remained limited, which makes today’s approval all the more significant.”

This approval is based on results of the pivotal Phase III INAVO120 study, 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<0.0001) in the first-line setting, demonstrating a statistically significant and clinically meaningful benefit. Overall survival (OS) data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 [boundary of 0.0098]). Follow-up for OS is continuing to the next analysis.

“We are thrilled by the approval of the Itovebi-based regimen, which is a huge step forward for advanced breast cancer patients with a PIK3CA mutation,” said Jean Sachs, CEO of Living Beyond Breast Cancer. “It remains critical that all patients have access to early, comprehensive biomarker testing so they can better understand what treatment options may be most beneficial for them and their tumour type.”

The Itovebi-based regimen was granted FDA Priority Review and Breakthrough Therapy Designation in May 2024 based on the INAVO120 study results. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency. Itovebi will be available in the US in the coming weeks. Early, comprehensive biomarker testing with an FDA-approved test, such as Foundation Medicine’s FoundationOne®Liquid CDx, can help identify people with HR-positive, HER2-negative breast cancer with a PIK3CA mutation.

Itovebi is currently being investigated in various combinations across three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer. We continue to evaluate opportunities to expand our clinical development programme to address patient unmet needs in various tumour types across oncology.