FDA Accepts NDA for Vepdegestrant in ESR1+ Advanced Breast Cancer

The FDA accepted vepdegestrant’s new drug application for ER+/HER2–, ESR1-mutated advanced breast cancer with a June 5, 2026, review date: © stock.adobe.com.

The U.S. Food and Drug Administration (FDA) has accepted a new drug application (NDA) highlighting vepdegestrant for the treatment of patients with estrogen receptor-positive (ER+) or human epidermal growth factor receptor 2-negative (HER2–), ESR1-mutated advanced or metastatic breast cancer who have previously received endocrine-based therapy, according to a news release from Arvinas.

In addition, the FDA has assigned a prescription drug user fee act (PDUFA) action date of June 5, 2026, which is a law that requires the FDA to review new cancer drugs within a set time to help get treatments to patients faster.

“Patients often face limited treatment options after first-line treatment and vepdegestrant demonstrated improved progression-free survival in patients with ESR1-mutated ER+/HER2– advanced breast cancer,” John Houston, chairperson, CEO, and president at Arvinas, said in the news release. “With the efficacy and favorable tolerability seen in VERITAC-2, we believe vepdegestrant, if approved, has potential to be a best-in-class treatment option for patients in the second-line ESR1-mutant setting. We look forward to working alongside Pfizer and with the FDA to pursue vepdegestrant’s approval and to ensure this important treatment option is made available to patients as rapidly as possible.”

The new drug application was based on data from VERITAC-2, a global, randomized phase 3 clinical trial comparing vepdegestrant with Faslodex (fulvestrant). These results were simultaneously presented at the 2025 American Society of Clinical Oncology Annual Meeting (ASCO) and published in The New England Journal of Medicine.

In the trial, vepdegestrant showed a significant and meaningful improvement in progression-free survival among patients with estrogen receptor 1 (ESR1) mutations, reducing risk of progression or death by 43% compared with Faslodex. Median progression-free survival assessed by blinded independent central review was 5 months with vepdegestrant versus 2.1 months with Faslodex. Investigator-assessed progression-free survival aligned with these results. The benefit was consistent across all pre-specified subgroups with ESR1 mutations. However, in the overall intent-to-treat population, the trial did not meet statistical significance for progression-free survival, with a median of 3.7 months for vepdegestrant and 3.6 months for Faslodex.

Vepdegestrant was generally well tolerated in the trial, with a safety profile consistent with previous studies and mostly low-grade treatment-emergent side effects. Rates and severity of gastrointestinal side effects were low with vepdegestrant (nausea, 13.5%; vomiting, 6.4%; diarrhea, 6.4%). Grade 4 (life-threatening) side effects occurred in five patients (1.6%) receiving vepdegestrant versus nine patients (2.9%) receiving Faslodex. The three most common side effects with vepdegestrant were fatigue (26.6%), increased alanine transaminase (14.4%) and increased aspartate aminotransferase (14.4%). Side effects leading to treatment discontinuation occurred in 2.9% of patients on vepdegestrant versus 0.7% on Faslodex.

Trial Design and Drug Information

The trial enrolled 624 patients at 213 sites in 25 countries, including 270 with ESR1 mutations. Patients were randomized equally to receive either vepdegestrant once daily by mouth on a continuous 28-day schedule or Faslodex by injection on Days 1 and 15 of the first cycle and then on Day 1 of each subsequent 28-day cycle starting with cycle 2. In total, 43% of patients had ESR1 mutations detected.

The primary goal was to evaluate progression-free survival in both the mutation-positive group and the overall population, based on a blinded independent central review. Overall survival was the key secondary endpoint.

Vepdegestrant is an experimental oral medication designed to break down estrogen receptors, which help fuel some breast cancers. It is being studied as a single treatment option for patients with advanced or metastatic breast cancer that is estrogen receptor positive and HER2 negative, especially those whose tumors have mutations in the ESR1 gene and have already received prior therapies.

References

1. “Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer,” Arvinas. News Release. August 8.
2. “Arvinas and Pfizer's Vepdegestrant Significantly Improves Progression-Free Survival for Patients with ESR1-Mutant, ER+/HER2- Advanced Breast Cancer,” Arvinas. News Release. May 31.

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