FDA Grants Priority Review to Giredestrant for ER+/HER2- Breast Cancer

The US FDA has accepted a new drug application (NDA) and granted priority review for giredestrant, an investigational oral selective estrogen receptor degrader (SERD), as an adjuvant treatment for adults with estrogen receptor (ER)-positive, HER2-negative, stage I to III breast cancer. The regulatory agency has set a Prescription Drug User Fee Act (PDUFA) action date of November 30, 2026. If approved, giredestrant would represent the first oral SERD to demonstrate a statistically significant clinical benefit in the curative, early-stage setting.¹

“Giredestrant represents the first major endocrine therapy advance in early-stage ER-positive breast cancer in decades, where the chance for cure is highest,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, in a news release. “The FDA’s filing acceptance brings us closer to delivering a new standard-of-care with the potential to fundamentally change the treatment paradigm for people with early-stage disease.”

The NDA filing is primarily supported by data from the phase 3 lidERA Breast Cancer clinical trial (NCT04961996), an open-label, randomized, multicenter study evaluating the efficacy and safety of adjuvant giredestrant compared with standard-of-care endocrine therapy. The trial enrolled over 4100 patients with medium- or high-risk stage I to III ER-positive, HER2-negative breast cancer.²

Interim analysis from the lidERA trial demonstrated that giredestrant reduced the risk of invasive disease recurrence or death (invasive disease-free survival [iDFS]) by 30% compared with standard endocrine regimens HR, 0.70; 95% CI, 0.57-0.87; P =.0014). At the 3-year landmark analysis, 92.4% of patients in the giredestrant cohort were alive and free of invasive disease, compared with 89.6% of patients receiving standard endocrine therapy. The observed iDFS benefit remained consistent across all prespecified, clinically relevant subgroups. Overall survival (OS) data were immature at the time of the analysis; however, investigators reported a positive trend, and follow-up will continue until the next planned interim analysis.

Safety data indicated that giredestrant was well tolerated, with an adverse event profile consistent with prior clinical experience. The treatment discontinuation rate due to adverse events was 5.3% in the giredestrant arm compared with 8.2% in the standard endocrine therapy arm.

ER-positive, HER2-negative disease constitutes approximately 70% of all breast cancer diagnoses globally. While the majority of these cases are identified at an early stage (stages I-III), up to one-third of patients eventually experience disease recurrence during or after standard adjuvant endocrine therapy. Tolerability issues with existing regimens frequently lead to premature treatment interruption or discontinuation, which significantly increases the long-term risk of recurrence and mortality.

About Giredestrant

Giredestrant is designed as a potent, next-generation oral SERD and full antagonist that competitively inhibits estrogen binding to its receptor, inducing receptor degradation and downregulating downstream signaling pathways to inhibit tumor cell proliferation.

In addition to the early-stage setting, the clinical development program for giredestrant extends into advanced disease paradigms. The FDA recently accepted a separate NDA for giredestrant in combination with everolimus for patients with ESR1-mutated, ER-positive advanced breast cancer, based on data from the evERA clinical trial (NCT05306340). A regulatory decision for that indication is anticipated in December 2026.³

Additional clinical trials within the giredestrant development program include the persevERA trial (NCT04546009) evaluating giredestrant plus palbociclib in endocrine-sensitive advanced disease; the pionERA trial (NCT06065748) evaluating giredestrant plus investigator's choice of CDK4/6 inhibitor in endocrine-resistant advanced disease; and the heredERA trial (NCT05296798) evaluating giredestrant in combination with dual HER2 blockade for ER-positive, HER2-positive advanced breast cancer.¹

REFERENCES

1. FDA Accepts New Drug Application for Genentech’s Giredestrant in ER-Positive Early-Stage Breast Cancer, the First and Only Oral SERD With Positive Phase III Results in the Curative Setting. News release. Genentech. June 2, 2026. Accessed June 2, 2026. https://tinyurl.com/yusbvayx

2. A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer). ClinicalTrials.gov. Updated May 22, 2026. Accessed June 2, 2026. https://clinicaltrials.gov/study/NCT04961996

3. FDA accepts new drug application for Genentech’s giredestrant in ESR1-mutated, ER-positive advanced breast cancer. News release. Genentech. February 19, 2026. Accessed June 2, 2026. https://tinyurl.com/ytf5t36m