Arvinas and Pfizer announced that their Phase 3 VERITAC-2 clinical trial of breast cancer candidate vepdegestrant has achieved its primary endpoint.
The primary endpoint was achieved following a statistically significant improvement shown in progression-free survival (PFS) for vepdegestrant in the oestrogen receptor 1-mutant (ESR1m) population compared to fulvestrant.
The trial focused on patients with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer. It highlighted that vepdegestrant, an investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader, exceeded the pre-specified hazard ratio target in the ESR1m subgroup.
However, the study did not reach statistical significance for PFS within the broader intent-to-treat population.
Pfizer oncology interim chief development officer Megan O’Meara said: “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 tumours harbour ESR1 mutations additional time without disease progression, compared to fulvestrant.”
At the time of analysis, less than 25% of required events for overall survival (OS) had occurred, rendering this data immature. The trial will continue to monitor overall survival as a key secondary endpoint.
Vepdegestrant was generally well tolerated, maintaining a safety profile consistent with previous trials.
Detailed results are set to be presented at an upcoming medical conference, which will facilitate global regulatory submissions.
Arvinas CEO and president John Houston said: “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 tumours harbour oestrogen receptor 1 mutations.”
Vepdegestrant’s development is a joint effort by Arvinas and Pfizer, aiming to harness the body’s protein disposal mechanisms to degrade oestrogen receptors.
This drug candidate is being explored as both a standalone and combination therapy for ER+/HER2- metastatic breast cancer. In February 2024, it received fast track designation from the US Food and Drug Administration (FDA) for potential use in patients previously treated with endocrine-based therapies.
The global VERITAC-2 study included 624 participants from 26 countries who had undergone prior treatment with CDK4/6 inhibitors and endocrine therapy.
Patients were assigned either daily oral vepdegestrant or intramuscular fulvestrant according to set dosing schedules.
In July 2021, Arvinas partnered with Pfizer for the co-development and co-commercialisation of vepdegestrant, sharing global development costs, commercial expenses, and profits. This collaboration seeks to advance therapeutic options for breast cancer patients globally.
