The US Food and Drug Administration (FDA) has approved Genentech’s Itovebi (inavolisib) for adults with hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation after endocrine therapy.
As per the approval, Itovebi will be administered in combination with palbociclib (Ibrance) and fulvestrant.
According to Genentech, Inavolisib is an oral therapy that demonstrates strong in vitro potency and selectivity in inhibiting PI3Kα, with the ability to specifically target and break down mutant PI3Kα protein.
Genentech, which is part of the Roche Group, secured approval based on the findings of the Phase 3 INAVO120 study. The late-stage trial demonstrated a 57% reduction in the risk of disease progression or death when treated with the Itovebi-based regimen compared to palbociclib and fulvestrant alone.
Although, the overall survival data is still under evaluation, a positive trend has been observed, and further follow-up is ongoing.
In May 2024, Itovebi received FDA priority review and breakthrough therapy designation based on the INAVO120 study results. Genentech is also submitting the data to health authorities in other regions, including the European Medicines Agency (EMA).
The INAVO120 trial involved 325 patients. The randomised, double-blind, placebo-controlled study assessed the safety and efficacy of Itovebi in combination with palbociclib and fulvestrant, compared to placebo with the same drugs.
The primary endpoint was progression-free survival, defined as the time from randomisation to either disease progression or patient death. Secondary endpoints included overall survival, objective response rate, and clinical benefit rate.
Patients in the study had HR-positive, HER2-negative, PIK3CA-mutated breast cancer that progressed during or within 12 months of adjuvant endocrine therapy, with no prior systemic therapy for metastatic disease. Participants were randomly assigned to receive either the investigational treatment or the placebo.
Genentech chief medical officer and global product development head Levi Garraway said: “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.
“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.”
Itovebi is expected to be available in the US within the next few weeks.
According to Genentech, early biomarker testing, such as Foundation Medicine’s FoundationOne Liquid CDx, is recommended to identify patients with the PIK3CA mutation, ensuring timely treatment decisions.
Genentech is also investigating Itovebi in various combinations across ongoing Phase 3 clinical trials targeting PIK3CA-mutated locally advanced or metastatic breast cancer.
