CHMP recommends EU approval of Itovebi for PIK3CA-mutated, ER-positive, HER2-negative, advanced breast cancer – Roche
Roche announced today that the EMA’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Itovebi (inavolisib), in combination with palbociclib (Ibrance) and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment. If approved, the Itovebi-based regimen has the potential to transform the standard of care in this first-line setting, where treatments are currently limited. A final decision regarding the approval is expected from the European Commission in the near future.
The CHMP’s positive opinion is based on the phase III INAVO120 results, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen 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. The PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, characterised as difficult-to-treat disease. The Itovebi-based regimen was well tolerated, with no new safety signals observed.
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.
Positive topline results from the final overall survival (OS) analysis, announced in January 2025, showed a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen. 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)). The full results from the OS analysis will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting.
“The positive CHMP recommendation for the Itovebi-based regimen represents a significant step towards providing people in the EU with PIK3CA-mutated, ER-positive advanced breast cancer with a targeted therapy in the first-line setting,” said Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. “This recommendation is further enforced by the recent final overall survival results from the INAVO120 study, showing the regimen can meaningfully extend survival.”
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.
