The FDA has approved vepdegestrant (Veppanu, Arvinas Operations) for the treatment of certain patients with ER-positive, HER2-negative advanced or metastatic breast cancer.

Specifically, the approval is for patients who have an ESR1 mutation as detected by an FDA-authorized test and who have experienced disease progression after one to two lines of endocrine therapy, including one line with a CDK4/6 inhibitor, according to the approval notice. 

The FDA also approved the Guardant360 CDx test as a companion diagnostic device to identify patients eligible for treatment.

Approval of vepdegestrant, a novel heterobifunctional protein degrader , and the companion diagnostic device was based on efficacy and safety demonstrated in the randomized, phase 3, open-label VERITAC-2 trial. 

Median progression-free survival (PFS) did not differ in the overall population of 624 ER-positive, HER2-negative patients who were randomized 1:1 to receive oral vepdegestrant or intramuscular fulvestrant (hazard ratio [HR], 0.83). However, among 270 patients with an ESR1 mutation, PFS was significantly longer in the vepdegestrant arm (5 vs 2.1 months; HR, 0.57); and the objective response rates were 19% and 4%, respectively.

Vepdegestrant was given at the recommended dose of 200 mg taken orally once daily with food until disease progression or unacceptable toxicity. Fulvestrant was administered on days 1 and 15 of cycle one and then once monthly thereafter.

Overall survival data were immature at the time of PFS analysis.

Findings from VERITAC-2 were presented at the 2025 American Society of Clinical Oncology annual meeting and were simultaneously published in The New England Journal of Medicine.

Full prescribing information for vepdegestrant, which includes warnings and precautions for QTc interval prolongation and embryo-fetal toxicity will be posted on Drugs@FDA.com.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDEdge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.