PRINCETON, N.J., August 31, 2026
PMV Pharmaceuticals announced updated interim data from the Phase 2 pivotal portion of the PYNNACLE clinical trial, highlighting continued development of rezatapopt as a potential targeted treatment for patients with advanced solid tumors carrying the TP53 Y220C mutation. In the ovarian cancer cohort, the company reported an overall response rate (ORR) of 46%, with 35 of 76 evaluable patients achieving a response based on investigator assessment using RECIST 1.1 criteria. The responses included four confirmed complete responses and 29 confirmed partial responses, while two additional partial responses remained unconfirmed at the data cutoff. The median time to response was 1.3 months, while the median duration of response among confirmed responders reached 10.0 months. PMV said enrollment of patients with platinum-resistant or platinum-refractory ovarian cancer for the primary analysis has now been completed, positioning the program for a more comprehensive clinical update later in 2026.
Rezatapopt Targets TP53 Y220C Mutation
The company is developing rezatapopt (PC14586) as a first-in-class small-molecule p53 reactivator designed to selectively bind the pocket created by the Y220C mutation in p53, with the goal of restoring the tumor-suppressor function of the altered protein. The updated ovarian cancer findings are particularly relevant because patients with platinum-resistant or platinum-refractory disease have limited treatment options and represent an important unmet medical need. PMV reported that rezatapopt continued to demonstrate a favorable and consistent safety and tolerability profile across the clinical program, with treatment-related adverse events predominantly reported as Grade 1 or Grade 2. The company also reported a 5% discontinuation rate due to treatment-related adverse events, while noting that the safety profile observed in the ovarian cancer cohort was generally consistent with the broader patient population. These findings provide additional clinical information as PMV evaluates the potential role of mutation-directed treatment in TP53 Y220C-positive cancers.
FDA Feedback Supports Accelerated Approval Strategy
PMV Pharmaceuticals also reported that a recent interaction with the U.S. Food and Drug Administration (FDA) provided feedback supporting the company’s strategy for pursuing an accelerated approval pathway for rezatapopt in patients with platinum-resistant or platinum-refractory ovarian cancer carrying the TP53 Y220C mutation. Based on the Phase 2 portion of PYNNACLE, the company currently plans to submit a New Drug Application (NDA) in the first quarter of 2027. The regulatory development represents an important next stage for the program, although the reported interim data do not yet constitute an FDA approval or establish that accelerated approval will ultimately be granted. PMV plans to present an update covering all PYNNACLE Phase 2 pivotal cohorts at a medical conference in the fourth quarter of 2026, including the primary analysis from the ovarian cancer cohort. The Phase 2 program is a multicenter, single-arm, registrational basket trial evaluating rezatapopt at 2,000 mg once daily across ovarian, lung, breast, endometrial and other solid tumors.
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PMV Builds Precision Oncology Pipeline Around p53
The PYNNACLE program represents the central clinical development effort for PMV Pharma’s precision oncology strategy, which focuses on therapeutics designed to address cancer-driving alterations in the p53 pathway. Rezatapopt has received FDA Fast Track designation for patients with locally advanced or metastatic solid tumors carrying a TP53 Y220C mutation, as well as Orphan Drug Designation for TP53 Y220C-positive ovarian, fallopian tube and primary peritoneal cancers. The company is now moving toward the next major data milestone while preparing for its planned 2027 NDA submission in ovarian cancer. With primary enrollment completed in the ovarian cohort and additional Phase 2 cohorts continuing to contribute data, upcoming clinical results will be important for determining whether the response signal observed to date can translate into a stronger regulatory case and broader development opportunity for rezatapopt.
Source: PMV Pharmaceuticals,, press relese
