E. E. Dumbrava, Geoffrey I. Shapiro, Aparna R. Parikh, Melissa L. Johnson, Anthony W. Tolcher, John A. Thompson, Anthony B. El-Khoueiry, A. Vandross, Shivaani Kummar, Dale R. Shepard, Kim LeDuke, Lisa Sheehan, Leila Alland, Arshad Haque, Deepika Jalota, Marc Fellous, Alison M. Schram
BACKGROUND: Rezatapopt is an investigational, first-in-class, oral, selective p53 reactivator that specifically binds to Y220C-mutated p53, which stabilizes p53 in its wild-type conformation and restores its functionality. METHODS: Y220C mutation to receive rezatapopt during continuous 21-day treatment cycles. The primary objectives were to determine the maximum tolerated dose and recommended phase 2 dose. Primary end points included dose-limiting toxic effects and adverse events. Secondary end points included preliminary efficacy and pharmacokinetic features. RESULTS: . CONCLUSIONS: In this phase 1 study involving heavily pretreated patients, the most common adverse events associated with rezatapopt were nausea and vomiting. Antitumor activity occurred across multiple tumor types, providing proof of concept for p53 reactivation. (Funded by PMV Pharmaceuticals; PYNNACLE ClinicalTrials.gov number, NCT04585750.).