FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Regulatory approval: On May 1, 2026, the FDA approved vepdegestrant (Veppanu), a heterobifunctional protein degrader, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer detected by an FDA-authorized test, after progression following at least one line of endocrine therapy. Approval was supported by VERITAC-2, where blinded independent central review–assessed PFS improved versus fulvestrant in the ESR1-mutated subgroup (median 5.0 vs 2.1 months; HR 0.57).
FDA approval: vepdegestrant in ESR1-mutated ER+/HER2− advanced/metastatic breast cancer
On May 1, 2026, the US FDA granted approval to vepdegestrant (Veppanu; Arvinas Operations, Inc.), a heterobifunctional protein degrader, for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy.
The FDA also approved Guardant360 CDx as a companion diagnostic to identify patients with ESR1 mutations for treatment with vepdegestrant.
Supporting trial evidence (VERITAC-2; NCT05654623)
VERITAC-2 was a randomized, open-label, active-controlled, multicenter trial (N=624), including 270 patients with ESR1-mutated tumors. Patients had progression on 1–2 lines of endocrine therapy, including one line with a CDK4/6 inhibitor, and were randomized 1:1 to vepdegestrant orally once daily or fulvestrant IM.
In the ESR1-mutated population, BICR-assessed PFS favored vepdegestrant: median 5.0 months (95% CI, 3.7–7.4) vs 2.1 months (95% CI, 1.9–3.5); HR 0.57 (95% CI, 0.42–0.77); p=0.0001. ORR was 19% vs 4%. OS was immature (16% deaths at the time of PFS analysis).
Safety and dosing (label highlights)
Warnings/precautions include QTc interval prolongation and embryo-fetal toxicity. Recommended dose: 200 mg orally once daily with food until disease progression or unacceptable toxicity.