FDA Approves Companion Diagnostic for Vepdegestrant in ESR1+, ER+/HER2-Negative Advanced Breast Cancer

The FDA has approved the Guardant360 CDx liquid biopsy test as a companion diagnostic for vepdegestrant (Veppanu) in the treatment of patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations.¹

On May 1, 2026, the FDA approved vepdegestrant for the treatment of adult patients 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 1 line of endocrine therapy.²

Guardant360 CDx is a non-invasive, blood-based test used to identify ESR1 mutations, allowing for potential treatment with vepdegestrant.¹

“This latest FDA approval using Guardant360 CDx reflects where cancer care is headed using blood-based testing to detect resistance earlier and guide smarter treatment decisions,” Helmy Eltoukhy, chairman and co-chief executive officer of Guardant Health, stated in a news release. “By identifying ESR1 mutations with just a simple blood draw, we’re helping bring more precise, personalized options to patients when they need them most.”

What data supported the FDA approval of vepdegestrant?

Vepdegestrant’s approval was backed by data from the phase 3 VERITAC-2 trial (NCT05654623), which demonstrated that patients harboring ESR1 mutations treated with vepdegestrant (n = 136) experienced a median progression-free survival (PFS) of 5.0 months (95% CI, 3.7-7.4) compared with 2.1 months (95% CI, 1.9-3.5) for those treated with fulvestrant (Faslodex; n = 134; HR, 0.57; 95% CI, 0.42-0.77; P = .0001).³

Within this subgroup, the confirmed objective response rate (ORR) was 19% (95% CI, 12%-27%) with vepdegestrant compared with 4% (95% CI, 1.6%-10%) with fulvestrant. No complete responses were reported in either arm.

How was VERITAC-2 designed?

The randomized, open-label, multicenter trial enrolled adult patients with ER-positive, HER2-negative advanced or metastatic breast cancer. Among 624 total patients included in the study, 270 had tumors harboring ESR1 mutations. For all patients, disease progression on 1 to prior line of endocrine therapy, including 1 line with a CDK4/6 inhibitor, was required. Notably, for patients who experienced disease progression during or within 12 months of completing adjuvant therapy, this one considered 1 line of prior endocrine therapy in the advanced/metastatic setting.

Prior treatment with chemotherapy in the advanced/metastatic setting or fulvestrant in any setting was not allowed. Patients who experienced disease progression within the first 6 months of starting their most recent line of endocrine therapy were also excluded.

Patients were randomly assigned 1:1 to receive vepdegestrant (n = 313) at 200 mg once per day or fulvestrant at 500 mg on days 1 and 15 of cycle 1, then once per month in subsequent cycles (n = 311). Treatment in both arms continued until disease progression or unacceptable toxicity. Patients were stratified by ESR1 mutation status (yes vs no) and visceral metastases status (yes vs no).

PFS per blinded independent central review in the overall and ESR1-mutated populations served as the trial’s primary end point. Secondary end points included overall survival and ORR.

What safety data were reported for vepdegestrant?

The most common adverse effects (AEs) reported in at least 10% of patients treated with vepdegestrant (n =312) included decreased white blood cell count, increased aspartate aminotransferase levels, musculoskeletal pain, fatigue, decreased hemoglobin levels, decreased neutrophil count, increased alanine aminotransferase levels, increased alkaline phosphatase levels, nausea, decreased blood potassium levels, increased bilirubin levels, decreased appetite, prolonged electrocardiogram QT, decreased platelet count, and constipation.

AEs led to permanent discontinuation of vepdegestrant in 2.9% of patients. The rates of dose interruptions and dose reductions due to AEs were 14% and 1.9%, respectively.

Serious AEs occurred in 9% of patients treated with vepdegestrant, which included any fracture (1.3%), fall (0.6%), hypercalcemia (0.6%), hepatic injury (0.6%), pneumonia (0.6%), musculoskeletal pain (0.6%), and prolonged QTc (0.3%). Fatal AEs were reported in 1.0% of patients, with dyspnea, cerebral ischemia, and unknown cause each leading to 1 death.

References

1. Guardant Health receives FDA approval for Guardant360 CDx as a companion diagnostic for Arvinas and Pfizer’s Veppanu (vepdegestrant) for patients with ER+/HER2- advanced breast cancer with ESR1 mutations. News release. Guardant Health. May 4, 2026. Accessed May 4, 2026. https://investors.guardanthealth.com/press-releases/press-releases/2026/Guardant-Health-Receives-FDA-Approval-for-Guardant360-CDx-as-a-Companion-Diagnostic-for-Arvinas-and-Pfizers-VEPPANU-vepdegestrant-for-Patients-with-ERHER2--Advanced-Breast-Cancer-with-ESR1-Mutations/default.aspx
2. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. FDA. May 1, 2026. Accessed May 4, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast
3. Veppanu. Prescribing information. Arvinas. Updated May 2026. Accessed May 4, 2026. https://www.arvinas.com/wp-content/uploads/2026/05/NDA-219835_Approval-Rx-ONLY.pdf