PMV Pharmaceuticals reported first‑in‑human data showing that rezatapopt, a small molecule designed to reactivate mutant p53, produced objective responses in heavily pretreated patients with TP53 Y220C–mutated solid tumors. The Phase I portion of the PYNNACLE trial, published in the New England Journal of Medicine, established a recommended Phase II dose and a tolerable safety profile. Investigators described antitumor activity across multiple histologies and biomarker signals consistent with selective binding of rezatapopt to the Y220C pocket and restoration of wild‑type p53 function. PMV plans registrational Phase II work and aims to file a New Drug Application in platinum‑resistant/refractory ovarian cancer in 2027. The NEJM publication provides peer‑reviewed proof‑of‑concept for reactivating a historically undruggable tumor suppressor in a genetically defined patient subset, supporting further development strategies that hinge on molecularly guided patient selection.