Arvinas, Inc. and Pfizer Inc. recently announced results from the randomized phase III VERITAC-2 clinical trial (ClinicalTrials.gov identifier NCT05654623) evaluating vepdegestrant monotherapy vs fulvestrant in adults with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer whose disease progressed after treatment with CDK4/6 inhibitors and endocrine therapy. Vepdegestrant (ARV-471) is an investigational, oral, first-in-class PROTAC (proteolysis-targeting chimera) estrogen receptor degrader.
The trial enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy. Patients were randomly assigned 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 trial met its primary endpoint in the ESR1-mutant population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival vs fulvestrant. The results exceeded the prespecified target hazard ratio of 0.60 in the ESR1-mutant population. The trial did not reach statistical significance in terms of improvement in progression-free survival in the intent-to-treat (ITT) population.
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 reported to be 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.
In February 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer previously treated with endocrine-based therapy.
