PMV Pharmaceuticals Announces Promising Rezatapopt Monotherapy Interim Data From PYNNACLE Phase 2 Trial Across Multiple Solid Tumors With a TP53 Y220C Mutation

Core Insights - PMV Pharmaceuticals announced interim data from the Phase 2 pivotal portion of the PYNNACLE clinical trial evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation [1][5][10] Efficacy - The Phase 2 clinical trial data as of August 4, 2025, showed an overall response rate (ORR) of 33% among 97 evaluable patients across all cohorts, with a median duration of response of 6.2 months [5][6] - In the ovarian cancer cohort, the ORR was 43% among 44 evaluable patients, with a median duration of response of 7.6 months [5][6] - Confirmed responses were observed in eight tumor types, including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder, and ampullary carcinoma [5][6] Safety - The safety population consisted of 109 patients treated with rezatapopt 2000 mg daily as monotherapy, with a median of three prior lines of systemic therapy [6] - Treatment-related adverse events (TRAEs) were mostly Grade 1-2, with the most frequent being nausea, fatigue, increased blood creatinine, and increased alanine aminotransferase [6] - The rate of drug discontinuations due to TRAEs was 3.7%, and all Grade 3 TRAEs resolved on treatment [6] Regulatory Update - PMV Pharma plans to submit a New Drug Application (NDA) for rezatapopt in platinum-resistant/refractory ovarian cancer by the end of the first quarter of 2027 [5][7] - The company aims to enroll an additional 20-25 patients with platinum-resistant/refractory ovarian cancer by the end of the first quarter of 2026 [7] About Rezatapopt - Rezatapopt (PC14586) is a first-in-class small molecule designed to selectively bind to the p53 Y220C mutant protein, restoring its tumor-suppressor function [9] - The FDA has granted Fast Track designation to rezatapopt for treating patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation [9] About the PYNNACLE Clinical Trial - The ongoing Phase 1/2 PYNNACLE clinical trial evaluates rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation, with the primary objective of assessing efficacy at the recommended Phase 2 dose [10]