Arvinas and Pfizer announced positive Phase 3 VERITAC-2 trial results for vepdegestrant, a novel oral PROTAC ER degrader for advanced or metastatic ER+/HER2- breast cancer. The trial demonstrated a statistically significant improvement in progression-free survival (PFS) in patients with an ESR1 mutation, a key driver of resistance to standard treatments. Vepdegestrant reduced the risk of disease progression or death by 43% compared to fulvestrant in this patient subgroup, with a median PFS of 5.0 months versus 2.1 months, respectively. While the trial did not meet statistical significance for PFS in the overall intent-to-treat population, the positive results in the ESR1 mutation subgroup are clinically meaningful.
This news is particularly important for patients with ER+/HER2- metastatic breast cancer who have progressed after CDK4/6 inhibitor and endocrine therapy, especially those with ESR1 mutations. These patients often face a poor prognosis and limited treatment options. Vepdegestrant offers a potential new therapy with a manageable safety profile, specifically targeting the mechanism driving their disease resistance. This targeted approach could significantly extend the time before further disease progression, improving quality of life and potentially overall survival.
The VERITAC-2 trial enrolled 624 patients across 26 countries. In the ESR1 mutation subgroup, vepdegestrant improved the clinical benefit rate to 42.1% versus 20.2% with fulvestrant and objective response rate to 18.6% versus 4.0%. Vepdegestrant also demonstrated a favorable safety profile with low rates of gastrointestinal side effects, a common issue with existing therapies. Data on overall survival, a key secondary endpoint, is still maturing. Arvinas and Pfizer plan to file a New Drug Application with the FDA in the second half of 2025.
These results mark a significant milestone for the field of targeted cancer therapies. Vepdegestrant is the first PROTAC to demonstrate positive Phase 3 results in any cancer type. Its success paves the way for further research and development of PROTACs for other challenging cancers, potentially revolutionizing how we treat various diseases driven by specific protein targets. A successful NDA submission and subsequent approval could position vepdegestrant as a critical new treatment option for patients with advanced or metastatic breast cancer, addressing a significant unmet medical need. This positive outcome could also drive further investment and innovation in the PROTAC platform, potentially expanding its applications across different therapeutic areas.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
