FDA accepts Genentech application for giredestrant in ESR1-mutated advanced breast cancer
The FDA has accepted the New Drug Application for giredestrant plus everolimus in ESR1-mutated, ER-positive, HER2-negative advanced breast cancer. The filing is based on Phase III evERA data showing reduced risk of disease progression or death versus standard-of-care endocrine therapy plus everolimus.
The U.S. Food and Drug Administration has accepted the New Drug Application for giredestrant in combination with everolimus for the treatment of adult patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated locally advanced or metastatic breast cancer following recurrence or progression on a prior endocrine-based regimen. The FDA is expected to make a decision on the approval by December 18, 2026, and the filing acceptance is based on Phase III evERA Breast Cancer study results.
The Phase III study showed that giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in the intention-to-treat and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. In the ESR1-mutated population, the median progression-free survival was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively, with a stratified hazard ratio of 0.38, 95% CI: 0.27-0.54, p-value=<0.0001. In the intention-to-treat population, the median progression-free survival was 8.77 months compared with 5.49 months in the giredestrant and comparator arms, respectively, with a hazard ratio of 0.56, 95% CI: 0.44-0.71, p-value=<0.0001.
Overall survival data were immature at the time of analysis, but a clear positive trend was observed in the intention-to-treat population, with a hazard ratio of 0.69, 95% CI: 0.47-1.00, p-value=0.0473, and in the ESR1-mutated population, with a hazard ratio of 0.62, 95% CI: 0.38-1.02, p-value=0.0566. Follow-up for overall survival will continue to the next analysis. Adverse events for the giredestrant combination were manageable and consistent with the known safety profiles of the individual medicines, and no unexpected safety findings were observed, including no photopsia.
Genentech said giredestrant plus everolimus could be the first and only oral selective estrogen receptor degrader combination approved in the post-cyclin-dependent kinase 4/6 inhibitor setting. Data from evERA are being used to support filing submissions to other global health authorities.
Giredestrant is an investigational, oral, selective estrogen receptor degrader being studied in early and advanced estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. New post-progression treatment analyses from evERA will be presented at the 2026 American Society of Clinical Oncology Annual Meeting, and the U.S. FDA recently accepted the New Drug Application for giredestrant based on the positive evERA data.
Genentech also said the lidERA Breast Cancer data have been submitted to the FDA after results shared in December 2025 demonstrated a 30% reduction in the risk of invasive disease recurrence or death in early breast cancer. Primary results from the persevERA study in combination with palbociclib as a first-line therapy in locally advanced or metastatic cancer will be presented after the company announced that the study did not meet its primary endpoint, although the giredestrant combination showed a numerical improvement in this patient population.