New England Journal of Medicine Publishes First-in-Human Rezatapopt Data Showing Selective Reactivation of Mutant p53 in Advanced Solid Tumors

Core Insights - PMV Pharmaceuticals announced the publication of Phase 1 results for rezatapopt in the New England Journal of Medicine, demonstrating its potential in treating advanced solid tumors with a TP53 Y220C mutation [1][2][4] Group 1: Study Results - The Phase 1 portion of the PYNNACLE clinical trial involved 77 heavily pretreated patients, focusing on safety, pharmacokinetics, and determining the maximum tolerated dose of rezatapopt [3][6] - Objective responses were observed across multiple tumor types, with clinical activity linked to selective binding to the Y220C pocket and restoration of wild-type p53 function [3] - The overall response rate (ORR) across all cohorts was 34% (35 out of 103 patients), with a 46% ORR (22 out of 48 patients) specifically in ovarian cancer [4] Group 2: Drug Information - Rezatapopt (PC14586) is a first-in-class small molecule designed to reactivate p53 by selectively binding to the p53 Y220C mutant protein [5] - The FDA has granted Fast Track designation to rezatapopt for treating locally advanced or metastatic solid tumors with a p53 Y220C mutation [5] Group 3: Future Plans - The company plans to submit a New Drug Application for rezatapopt in platinum-resistant/refractory ovarian cancer in the first quarter of 2027 [4] - The ongoing Phase 2 portion of the PYNNACLE trial aims to evaluate the efficacy of rezatapopt in various solid tumors with TP53 Y220C and KRAS wild-type mutations [6]