FDA Approves Vepdegestrant for Breast Cancer With ESR1 Mutation

Vepdegestrant reduced disease progression risk by 43% in ESR1-mutated advanced breast cancer compared to fulvestrant.

Vepdegestrant has been approved for adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated advanced or metastatic breast cancer that progressed after at least one line of endocrine therapy (1^✔ ✔Trusted Source
FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

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On May 1, 2026, the Food and Drug Administration granted approval for vepdegestrant (Veppanu, Arvinas Operations, Inc.), a heterobifunctional protein degrader, for patients identified through an authorized diagnostic test.

The FDA also approved Guardant360 CDx as a companion diagnostic device to help identify breast cancer patients carrying ESR1 mutations who may benefit from treatment with vepdegestrant.

Breast Cancer Trial Focuses on ESR1 Mutations

Efficacy and safety were assessed in VERITAC-2, a randomized, open-label, active-controlled, multicenter trial involving 624 adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced or metastatic breast cancer.

• Among these participants, 270 patients had tumors with ESR1 mutations.
• Eligible participants experienced disease progression after one to two lines of endocrine therapy, including one line containing a cyclin-dependent kinase 4 and 6 inhibitor.
• Participants were randomly assigned in a 1:1 ratio to receive either oral vepdegestrant once daily or intramuscular fulvestrant on Days 1 and 15 during Cycle 1, followed by monthly dosing.

Randomization was based on ESR1 mutation status and the presence of visceral metastasis. ESR1 mutation status was determined using circulating tumor deoxyribonucleic acid blood testing performed centrally or locally.

Progression-Free Survival Improved With Vepdegestrant

The primary efficacy endpoint was progression-free survival assessed through blinded independent central review in patients with ESR1-mutated tumors and in the overall study population.

Additional efficacy measures included overall survival and objective response rate evaluated by blinded independent central review.

• Among patients with ESR1-mutated tumors, vepdegestrant demonstrated a statistically significant improvement in progression-free survival compared with fulvestrant.
• Median progression-free survival reached 5 months in the vepdegestrant group, compared with 2.1 months in the fulvestrant group.
• The hazard ratio was 0.57 with a p-value of 0.0001.
• Objective response rates were 19% for vepdegestrant and 4% for fulvestrant.

Overall survival findings remained immature, with 16% of deaths recorded in this patient population during the progression-free survival analysis.

Safety Warnings Linked to Vepdegestrant Treatment

The prescribing information for vepdegestrant contains warnings and precautions related to QTc interval prolongation and embryo-fetal toxicity.

The recommended dosage of vepdegestrant is 200 milligrams taken orally once daily with food until disease progression or unacceptable toxicity occurs.

The review process included the use of the Assessment Aid, a voluntary submission tool provided by the applicant to support the FDA’s evaluation. The application received approval one month earlier than the agency’s target decision date.

In conclusion, vepdegestrant received FDAapproval for ESR1-mutated advanced or metastatic breast cancer after demonstrating improved progression-free survival and response rates compared with fulvestrant in clinical testing.

Reference:

1. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer – (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast)

Source-Medindia