FDA Approves Vepdegestrant for Patients With ER-Positive, HER2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer
Clinical Summary:
- The US FDA approved vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced breast cancer after ≥1 prior endocrine therapy, based on the phase 3 VERITAC-2 trial.
- Vepdegestrant significantly improved progression-free survival and response rates in patients with ESR1-mutated disease compared with fulvestrant. Overall survival data remain immature.
- Vepdegestrant provides a new oral treatment option for patients with ESR1-mutated breast cancer, with companion diagnostic testing required to guide use.
On May 1, 2026, the US Food and Drug Administration (FDA) approved vepdegestrant (Veppanu; Arvinas Operations, Inc.) for adult patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer following disease progression on at least 1 line of endocrine therapy. This approval was based on results from the phase 3 VERITAC-2 trial.
In this multicenter, open-label trial, 624 patients were randomized 1:1 to receive either once daily vepdegestrant or intramuscular fulvestrant on days 1 and 15 of cycle 1 followed by once monthly thereafter. Patients were required to have received ≤2 prior lines of endocrine therapy, including a CDK4/6 inhibitor.
The primary end point was progression-free survival (PFS), as assessed by blinded independent central review, in patients harboring ESR1-mutations (n = 271). Key secondary end points included overall survival (OS), objective response rate (ORR), and safety.
At analysis, median PFS was 5 months in the vepdegestrant arm and 2.1 months in the fulvestrant arm (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = .0001). The ORR was 19% in the vepdegestrant arm and 4% in the fulvestrant arm. OS data were immature at PFS analysis.
The safety profile of vepdegestrant included warnings for QTc interval prolongation and embryo-fetal toxicity. The recommended dose is 200 mg taken orally once daily with food until disease progression or unacceptable toxicity.
The FDA has also approved the Guardant360 CDx as a companion diagnostic device to identify patients with breast cancer with ESR1 mutations eligible for treatment with vepdegestrant.
Source:
US Food and Drug Administration. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Accessed on May 1, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast
