FDA Approves Vepdegestrant for Advanced ESR1-Mutated ER+/HER2− Breast Cancer

The Food and Drug Administration (FDA) approved vepdegestrant (Veppanu, Arvinas Operations, Inc.) on May 1, 2026, for adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer whose disease progressed after at least 1 line of endocrine therapy. The ESR1 mutation must be detected with an FDA-authorized test.

The agency also approved Guardant360 CDx as a companion diagnostic for identifying patients with breast cancer who have ESR1 mutations. Vepdegestrant, which the FDA described as a heterobifunctional protein degrader, is administered at 200mg orally once daily with food until disease progression or unacceptable toxicity.

Approval was based on VERITAC-2 (NCT05654623), a randomized, open-label, active-controlled, multicenter trial involving 624 adults with ER-positive, HER2-negative advanced or metastatic breast cancer. Of those participants, 270 had tumors carrying ESR1 mutations. Participants had experienced disease progression after 1 or 2 lines of endocrine therapy, including 1 line with a CDK4/6 inhibitor. They were assigned 1:1 to daily oral vepdegestrant or intramuscular fulvestrant.

Among participants with ESR1-mutated tumors, median progression-free survival assessed by blinded independent central review was 5.0 months with vepdegestrant and 2.1 months with fulvestrant (hazard ratio, 0.57; 95% CI, 0.42-0.77; P=.0001). Objective response rates were 19% (95% CI, 12%-27%) and 4% (95% CI, 1.6%-10%), respectively. Overall survival data remained immature, with deaths occurring in 16% of patients at the time of the progression-free survival analysis.

The prescribing information includes warnings and precautions concerning QTc interval prolongation and embryo-fetal toxicity. The FDA approved the application 1 month ahead of the agency’s goal date.

Sources: FDA. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Accessed July 29, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast