PMV Pharmaceuticals' Cancer Drug Shows Promising Interim Data in Phase 2 Trial

PMV Pharmaceuticals reported interim data from the Phase 2 pivotal portion of the PYNNACLE clinical trial for its cancer drug rezatapopt. Confirmed responses were observed in patients with advanced solid tumors harboring a TP53 Y220C mutation in eight tumor types. The overall response rate was 33%, with a median time to response of 1.4 months and a median duration of response of 6.2 months. Treatment-related adverse events were mainly grade 1-2, with the most frequent being nausea, fatigue, increased blood creatinine, and increased alanine aminotransferase. PMV Pharma plans to submit an NDA for platinum-resistant/refractory ovarian cancer by the end of the first quarter of 2027.

PRINCETON, N.J., Sept. 10, 2025 — PMV Pharmaceuticals, Inc. (NASDAQ: PMVP), a precision oncology company, announced interim data from the Phase 2 pivotal portion of the PYNNACLE clinical trial for its cancer drug rezatapopt. The data, presented on September 10, 2025, demonstrated significant efficacy and a manageable safety profile in patients with advanced solid tumors harboring a TP53 Y220C mutation.

The Phase 2 PYNNACLE trial evaluated rezatapopt in patients with TP53 Y220C-mutated advanced solid tumors. The interim results showed a 33% overall response rate (ORR) across 97 evaluable patients, with confirmed responses in eight different tumor types. Key highlights include a 43% ORR in ovarian cancer patients, with a median duration of response of 7.6 months. The trial also demonstrated a 60% response rate in endometrial cancer, albeit in a small sample size of five patients.

The safety profile of rezatapopt was generally manageable, with predominantly Grade 1-2 treatment-related adverse events. The most frequent adverse events were nausea, fatigue, increased blood creatinine, and increased alanine aminotransferase. The discontinuation rate due to adverse events was low at 3.7%.

PMV Pharma plans to enroll an additional 20-25 platinum-resistant/refractory ovarian cancer patients and submit a New Drug Application (NDA) in the first quarter of 2027. The company expects to complete enrollment in the Phase 2 portion of the PYNNACLE study by the first quarter of 2026.

The interim data from the PYNNACLE trial positions rezatapopt as a potentially first-in-class p53-targeting therapy with promising clinical validation. The observed efficacy across eight tumor types suggests a substantial addressable market beyond just ovarian cancer. The 33% overall response rate provides proof-of-concept for PMV's precision oncology approach targeting the specific Y220C mutation of TP53. The 43% response rate in ovarian cancer, including one complete response, represents a compelling potential first approval pathway.

The clear regulatory guidance from the FDA provides a defined pathway to market. The company plans to enroll an additional 20-25 platinum-resistant/refractory ovarian cancer patients and submit an NDA by Q1 2027. This focused approach in a high unmet need population could potentially lead to an accelerated approval.

From a competitive standpoint, successfully targeting p53 would represent a significant innovation. Despite p53 mutations being present in approximately 50% of all cancers, effective therapies targeting this pathway have been elusive. Rezatapopt's mutation-specific approach demonstrates how precision medicine can address previously "undruggable" targets. The tumor-agnostic efficacy also suggests potential for label expansion across multiple indications following initial approval.

PMV Pharma will host an investor webinar on September 10, 2025, at 8:00 AM ET to review the PYNNACLE Phase 2 interim data and provide a regulatory update. The event will feature presentations by PMV Pharma management and Ramez N. Eskander, M.D., Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Diego.

Rezatapopt (PC14586) is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type tumor-suppressor function. The U.S. Food and Drug Administration granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation.

The PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the clinical trial was to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of rezatapopt when administered orally to patients. Safety, tolerability, pharmacokinetics, and effects on biomarkers were also assessed. The Phase 2 portion is a registrational, single arm, expansion basket clinical trial comprising five cohorts (ovarian, lung, breast, and endometrial cancers, and other solid tumors) with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C and KRAS wild-type advanced solid tumors.

PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53. TP53 mutations are found in approximately half of all cancers. The Company’s co-founder, Dr. Arnold Levine, established the field of p53 biology when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize more than four decades of p53 biology, PMV Pharma combines unique biological understanding with a pharmaceutical development focus.

Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s clinical development activities, plans and projected timelines for rezatapopt, including expectations regarding the timing and completion of patient enrollment and ultimate completion of the Phase 2 portion of the PYNNACLE study, the timing of disclosures regarding clinical data updates of its current clinical trial for rezatapopt, expected therapeutic benefits of rezatapopt including potential efficacy and tolerability, plans regarding regulatory filings and approvals, including targeted timelines for the Company’s New Drug Application submission and initial U.S. Food and Drug Administration (FDA) approval for platinum-resistant or refractory ovarian indication, ongoing safety and response rate of participants in the PYNNACLE study, as well as the overall timing and success of the Company’s current and future clinical trials for rezatapopt, the adequacy of the data to support the Company’s pursuit of regulatory approval, and the Company’s expectations regarding the therapeutic, addressable patient populations, timing for approval, and commercial potential of rezatapopt. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the Company’s preclinical studies and clinical trials may not be successful; the FDA may not agree with the Company’s interpretation of the data from clinical trials of its product candidates; the Company may decide, or the FDA may require the Company, to conduct additional clinical trials or to modify its ongoing clinical trials, which could result in enrollment or other delays to the Company’s anticipated timelines; the Company may experience delays in the commencement, enrollment, completion, or analysis of clinical testing for its PMV Pharmaceuticals Announces Promising Rezatapopt Monotherapy Interim Data From PYNNACLE Phase 2 Trial Across Multiple Solid Tumors With a TP53 Y220C Mutation^[1].