FDA Approves Vepdegestrant in ER+, HER2–, ESR1-Mutated Breast Cancer

The FDA has approved vepdegestrant (Veppanu) for patients with estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, which is detected with an FDA-authorized test, according to a press release from the agency.¹

Additionally, the FDA has approved the Guardant360 CDx as a companion diagnostic, which will help to identify patients with an ESR1 mutation. The approval is based on results from the phase 3 VERITAC-2 trial (NCT05654623), which assessed vepdegestrant monotherapy in patients with advanced metastatic breast cancer.²

Topline data included a median progression-free survival (PFS) of 5 months (95% CI, 3.7-7.4) in the vepdegestrant arm vs 2.1 months (95% CI, 1.9-3.5) in the fulvestrant (Faslodex) arm (HR, 0.57; 95% CI, 0.42-0.77; P = .0001). The objective response rate was 19% (95% CI, 12%-27%) vs 4% (95% CI, 1.6%-10.%), respectively. The overall survival data are still immature.

Patients were randomly assigned 1:1 to either receive vepdegestrant orally once daily or fulvestrant intramuscularly on days 1 and 15 during cycle 1 followed by monthly thereafter.

The prescribing information includes warnings and precautions for QTc interval prolongation and embryo-fetal toxicity.

The recommended doseage is 200 mg orally once daily with food.

References

1. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. May 1, 2026. Accessed May 1, 2026. https://tinyurl.com/yzf47dj2
2. Hamilton E, De Laurentiis M, Jhaveri K, et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study. J Clin Oncol. 2025;43(suppl 17):LBA1000. doi:10.1200/JCO.2025.43.17_suppl.LBA1000