Among patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer whose disease progressed following prior treatment with cyclin-dependent kinase 4/6 inhibitors and endocrine therapy, positive topline results have been announced from the phase 3 VERITAC-2 clinical trial, which met its primary goal evaluating vepdegestrant monotherapy versus Faslodex (fulvestrant), according to a news release from Arvinas and Pfizer Inc.
“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,” Dr. Megan O’Meara, Interim Chief Development Officer, Pfizer Oncology, said in the news release. “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 [Faslodex].”
This marks the first pivotal data for vepdegestrant, a potential first-in-class investigational oral PROteolysis Targeting Chimera (PROTAC) ER degrader, as per the release.
The trial met its primary end goal in the estrogen receptor 1-mutant (ESR1m) population, showing a statistically significant and clinically meaningful improvement in progression-free survival over Faslodex, with a greater than 40% reduction in the risk of disease progression or death. The trial did not reach statistical significance for progression-free survival improvement in the intent-to-treat population.
Furthermore, overall survival was immature at analysis, with fewer than one-fourth of required events. The trial will continue assessing overall survival as a key secondary endpoint. Vepdegestrant was generally well tolerated, with a safety profile consistent with previous studies. Detailed VERITAC-2 results will be submitted for presentation at a medical meeting this year and shared with global regulators to support potential filings.
In February 2024, the Food and Drug Administration granted fast track designation to vepdegestrant monotherapy for treating adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy, the companies announced.
“The first phase 3 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,” John Houston, Chairperson, Chief Executive Officer and President at Arvinas, said in the release. “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.”
Findings come from the global phase 3 VERITAC-2 trial which evaluated vepdegestrant as a monotherapy versus Faslodex in patients with ER+/HER2- advanced or metastatic breast cancer. The randomized study enrolled 624 patients across 26 countries who previously received a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy.
Patients were assigned to receive either oral vepdegestrant once daily on a 28-day continuous schedule or intramuscular Faslodex on days 1 and 15 of cycle 1, then on day 1 of each subsequent 28-day cycle. The primary end goal is progression-free survival in the intent-to-treat and ESR1m populations, as assessed by blinded independent central review.
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