About VERITAC-2 Trial

About the VERITAC-2 Trial

The VERITAC-2 trial was a Phase 3, randomized, open-label study evaluating vepdegestrant — an oral PROTAC (Proteolysis Targeting Chimera) estrogen receptor degrader developed by Arvinas and Pfizer — versus fulvestrant in patients with ER+/HER2− metastatic breast cancer who had progressed on CDK4/6 inhibitor-based therapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR), with secondary endpoints including overall survival (OS), objective response rate (ORR), and safety. In the key ESR1-mutant subgroup, vepdegestrant demonstrated a statistically significant improvement in PFS over fulvestrant (5.0 vs. 2.1 months; HR 0.58; p < 0.001), representing a 43% reduction in the risk of progression or death and marking the first positive Phase 3 data for any PROTAC degrader in oncology. No significant PFS benefit was observed in the intent-to-treat population, confining the drug's potential utility to ESR1-mutant patients. The treatment showed a notably favorable tolerability profile, with discontinuations and dose reductions occurring in fewer than 5% of patients, though QTc prolongation was observed in approximately 10% of those receiving vepdegestrant. These results were simultaneously presented at the ASCO Annual Meeting 2025 and published in the New England Journal of Medicine, and were discussed by key opinion leaders including Dr. Erika Hamilton — the trial's lead investigator — as well as Dr. Sara Tolaney, Dr. Harold Burstein, and Dr. Stephanie Graff, who highlighted both the significance of the ESR1-mutant PFS benefit and the open questions around OS maturity and the drug's positioning within an increasingly competitive second-line endocrine therapy landscape.