The PYNNACLE Phase 2 trial assessing rezatapopt, a selective p53 reactivator, in patients with advanced or metastatic solid tumors harboring a TP53 Y220C mutation: Interim analysis of patients with ovarian cancer

In this OncLive Rapid Readout, Alison Schram, MD, of Memorial Sloan Kettering Cancer Center, reviews interim findings from the phase 2 PYNNACLE trial evaluating rezatapopt, an investigational first-in-class selective p53 activator, in patients with advanced or metastatic solid tumors harboring TP53 Y220C mutations. Focusing on the ovarian cancer cohort, Schram highlights outcomes in 76 heavily pretreated patients, most of whom had high-grade serous ovarian cancer and platinum-resistant or platinum-refractory disease. Single-agent rezatapopt achieved an overall response rate of 44.4%, with responses observed across key subgroups, including prior bevacizumab exposure, prior PARP inhibitor use, and folate receptor status. The median time to response was 1.3 months, and the median duration of response was 8.2 months. Treatment-related adverse events were generally grade 1 or 2, and only 5% of patients discontinued therapy because of toxicity, supporting rezatapopt as a promising chemotherapy-free targeted option.