Agency Arvinas announces Federal Drug Administration acceptance of Vepdegestrant's New Drug Application for tackling ESR1m-positive, ER+/HER2- advanced breast cancer treatment.
In a significant development for patients with ER+/HER2- advanced or metastatic breast cancer, the Phase 3 VERITAC-2 clinical trial (NCT05654623) is evaluating a potential new treatment option. Vepdegestrant (ARV-471), a PROTAC estrogen receptor degrader, is being compared to fulvestrant in patients who have previously been treated with a CDK4/6 inhibitor plus endocrine therapy.
The trial, which enrolled 624 patients at 213 sites in 25 countries, randomised patients 1:1 to receive either vepdegestrant or fulvestrant. The primary endpoint of the trial is progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations, as determined by blinded independent central review.
In the ESR1-mutated subgroup, vepdegestrant demonstrated a significant clinical benefit over fulvestrant. The median PFS for vepdegestrant was 5.0 months, compared to just 2.1 months for fulvestrant (HR 0.58; P<0.001). This improvement was reflected in higher 6-month PFS rates (45.2% vs. 22.7%) and a superior objective response rate (ORR) of 18.6% versus 4.0% for fulvestrant.
However, in the overall patient population, no statistically significant PFS difference was observed (3.8 vs. 3.6 months; P=0.07). This underscores the importance of biomarker-driven therapy selection. The clinical benefit rate (CBR) was notably higher with vepdegestrant (42.1% vs. 20.2%).
Vepdegestrant was generally well tolerated, with mostly mild to moderate adverse events such as fatigue, mild liver enzyme elevations, and nausea. Serious adverse events (grade ≥3) occurred in 23.4% of patients, and treatment discontinuations were rare (2.9%).
These results establish vepdegestrant as the first PROTAC therapy to demonstrate Phase 3 benefit in breast cancer, offering a targeted oral option particularly for patients with ESR1-mutated disease who have progressed after endocrine therapy and CDK4/6 inhibitors. The FDA has accepted the new drug application based on these findings, supporting vepdegestrant’s potential to become a best-in-class treatment option in this setting.
Arvinas, a clinical-stage biotechnology company headquartered in New Haven, Connecticut, is progressing multiple investigational drugs through clinical development programs, including vepdegestrant, ARV-393, ARV-102, and ARV-806. The company is dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases.
The press release contains forward-looking statements regarding vepdegestrant's potential as a treatment option for patients with ER+/HER2- advanced or metastatic breast cancer with ESR1 mutations in the second line-plus setting, and vepdegestrant's potential approval and availability to patients. However, the risks and uncertainties associated with these forward-looking statements include, but are not limited to, the successful performance of obligations under the collaboration between Arvinas and Pfizer, the ability to successfully conduct and complete clinical development for vepdegestrant as a monotherapy, the ability to meet the secondary endpoint for overall survival in the trial, and the risks related to regulatory applications and approvals.
Science has made a significant stride in health and wellness, particularly for patients with ER+/HER2- advanced or metastatic breast cancer. A new medical-condition-focused treatment option, vepdegestrant (a PROTAC estrogen receptor degrader), shows promising results in the trial VERITAC-2, specifically for patients with ESR1-mutated breast cancer who have progressed after endocrine therapy and CDK4/6 inhibitors. breast-cancer patients with ESR1 mutations may benefit from vepdegestrant, as it demonstrated a significant clinical benefit over the existing treatment, fulvestrant, with a median PFS of 5.0 months compared to just 2.1 months for fulvestrant.
