Positive Results for Vepdegestrant in Phase III Trial

These are the first pivotal data for vepdegestrant, a potential first-in-class investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader.

The Phase III VERITAC-2 clinical trial (NCT05654623) ,  a global randomized study enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.  

Patients were randomized to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. The primary endpoint was progression-free survival (PFS) in the intent-to-treat and ESR1m populations as determined by blinded independent central review. Overall survival is a key secondary endpoint.

Overall survival was not mature at the time of the analysis, with less than a quarter of the required number of events having occurred. The trial will continue to assess overall survival as a key secondary endpoint. In the trial, vepdegestrant was generally well tolerated and its safety profile was consistent with what has been observed in previous studies. Detailed results from VERITAC-2 will be submitted for presentation at a medical meeting later this year, and these data will be shared with global regulatory authorities to potentially support regulatory filings.

“The first Phase III data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations,” said Dr. John Houston,  Chairman, Chief Executive Officer and President at Arvinas. “We want to thank the patients and investigators who participated in this trial, and we look forward to sharing these data with health authorities as well as at a medical conference in 2025.”

 "Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies,” said Dr. Megan O’Meara, Interim Chief Development Officer, Pfizer Oncology. “These data from VERITAC-2 support the potential of vepdegestrant to give patients whose tumors harbor ESR1 mutations additional time without disease progression, compared to fulvestrant."

Vepdegestrant is an investigational oral PROTAC ER degrader for ER+/HER2- breast cancer being jointly developed by Arvinas and Pfizer and is designed to harness the body’s natural protein disposal system to specifically target and degrade the ER. In February 2024, the companies announced that the FDA  granted Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.