Arvinas, Inc. and Pfizer Inc. reported positive topline results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) comparing fulvestrant and vepdegestrant monotherapy in adults with advanced or metastatic breast cancer that is estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-) and whose disease progressed after cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy. Vepdegestrant, a possible first-in-class investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader, has these initial pivotal findings.
In the population with estrogen receptor 1-mutant (ESR1m), the trial achieved its primary aim, showing a statistically significant and clinically relevant improvement in progression-free survival (PFS) when compared to fulvestrant. The outcomes in the ESR1m population were higher than the predetermined goal hazard ratio of 0.60. The intent-to-treat (ITT) population’s PFS did not improve to a statistically significant level during the trial.
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,
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.
John Houston
At the time of the analysis, less than 25% of the necessary number of events had taken place, indicating that overall survival was not mature. Overall survival will be evaluated as a crucial secondary objective throughout the experiment. Vepdegestrant was generally well tolerated during the trial, and its safety profile aligned with findings from earlier research. In-depth findings from VERITAC-2 will be shared with international regulatory bodies to perhaps assist regulatory filings, and they will be presented at a medical conference later this year.
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,
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.
Megan O’Meara
Arvinas and Pfizer are working together to develop Vepdegestrant, an experimental oral PROTAC ER degrader for ER+/HER2- breast cancer. It works by using the body’s built-in protein disposal mechanism to target and precisely degrade the ER. The companies declared in February 2024 that the FDA had given Fast Track designation to the study of vepdegestrant as a monotherapy for adults with metastatic or ER+/HER2-advanced breast cancer who had previously received endocrine-based therapy.
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VERITAC-2 Clinical Trial
In patients with ER+/HER2-advanced or metastatic breast cancer, the Phase 3 VERITAC-2 clinical trial (NCT05654623) is a worldwide randomized study comparing the safety and effectiveness of vepdegestrant (ARV-471) as a monotherapy to fulvestrant. 624 individuals who had previously undergone treatment with a CDK4/6 inhibitor in addition to endocrine therapy were recruited for the trial from locations spread across 26 nations.
Patients were randomly assigned to receive either fulvestrant, which was given intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle beginning on Day 1 of Cycle 2, or vepdegestrant, which was given orally once daily on a 28-day continuous dosing schedule. Progression-free survival (PFS) in the ESR1m and intent-to-treat groups, as assessed by blinded independent central review, was the main outcome. One important secondary endpoint is overall survival.
Source: Pfizer
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