Arvinas and Pfizer Announce First Positive Phase 3 Results for PROTAC Degrader Vepdegestrant in ESR1-Mutated Breast Cancer

On March 11, Arvinas (Nasdaq:ARN) and PfizerPositive results from the VERITAC-2 Phase 3 clinical trial (NCT05654623) were announced. The trial evaluated the efficacy in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic cancer whose disease had progressed after prior treatment with a CDK4/6 inhibitor and endocrine therapy.Ren Zhong，vepdegestrantMonotherapy andFluorouracilFulvestrantTreatmentTherapeuticEfficacy. These are the first critical data of vepdegestrant,Vepdegestrant is a potentialfirst-in-classOral PROTAC ER Degrader.

The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant. In the ESR1m population, the results exceeded the pre-specified target hazard ratio of 0.60.The trial did not achieve statistical significance in PFS improvement within the intent-to-treat (ITT) population.

Arvinas Chairman, CEO and President John Houston, Ph.D., said:"The first Phase 3 data readout for a PROTAC degrader represents a significant achievement, with the data indicating thatVepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic cancer harboring estrogen receptor 1 mutations in their tumors. We would like to thank the patients and researchers involved in this trial, and we look forward to sharing these data with health authorities and at a medical conference in 2025.

At the time of analysis, overall survival was not yet mature, with less than a quarter of the required events having occurred. The trial will continue to evaluate overall survival as a key secondary endpoint. In the trial,Vepdegestrant was generally well-tolerated, with a safety profile consistent with what has been observed in prior studies. Detailed results from VERITAC-2 will be presented at a medical conference later this year, and the data will be shared with global regulatory authorities to potentially support regulatory filings.

Megan O'Meara, M.D., Interim Chief Development Officer of Pfizer Oncology, stated:"Patients with late-stage ER+/HER2- metastatic cancer face significant clinical challenges, with limited treatment options after disease progression and the development of resistance to existing endocrine therapies. Compared to fulvestrant, these data from VERITAC-2 support..."Vepdegestrant has the potential to provide additional time without disease progression for patients with tumors carrying ESR1 mutations.

Vepdegestrant is an investigational oral PROTAC ER degrader jointly developed by Arvinas and Pfizer for the treatment of ER+/HER2- breast cancer, aiming to utilize the body's natural protein processing system to specifically target and degrade ER. In February 2024, the two companies announced that the U.S. FDA granted Vepdegestrant Fast Track designation for the study of monotherapy in adults with ER+/HER2- advanced or metastatic breast cancer who have previously received endocrine therapy.