Pfizer and Arvinas released topline data from the Phase III trial evaluating its estrogen receptor (ER) degrader, vepdegestrant, in patients with breast cancer.
The ‘first pivotal data readout for a PROTAC (PROteolysis TArgeting Chimera) therapy’ proved to be a mixed bag. Vepdegestrant was unable to show an improvement in progression-free survival (PFS) in the intent-to-treat population, only meeting the trial’s primary endpoint of PFS improvement in the estrogen receptor 1-mutant (ESR1m) population.
Following the news, Arvinas’ stock was down by 21.55% at market close on 11 March, compared to the market open on the same day. Pfizer’s stock fared better, falling by 2.18% during the same period.
Phase III trial data
The open-label Phase III evaluated vepdegestrant against AstraZeneca’s Faslodex (fulvestrant) in 624 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer who had previously received treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy.
ClinicalTrial.gov notes the study’s endpoint as improvement in PFS or death due to any cause. The trial failed to meet its primary endpoint in the intent-to-treat (ITT) population. But the companies were quick to note that vepdegestrant demonstrated a ‘statistically significant and clinically meaningful’ improvement in PFS in ESR1m population, compared to Faslodex.
The companies did not report overall survival, the trial’s key secondary endpoint, noting it was “not mature at the time of the analysis, with less than a quarter of the required number of events having occurred”. Pfizer and Arvinas plan to share the detailed results at a later date in a medical meeting, and intend to share these with “global regulatory authorities to potentially support regulatory filings”.
The companies reported that vepdegestrant was “generally well tolerated and its safety profile was consistent with what has been observed in previous studies”.
Other approved therapies for treating advanced breast cancer include Eli Lilly’s Verzenio (abemaciclib), Pfizer’s Ibrance (palbociclib), and Novartis’ Kisqali (ribociclib).
