Rezatapopt Yields Responses, Supports NDA Plan in Ovarian Cancer

Updated interim data from the ovarian cancer cohort of the phase 2 PYNNACLE trial (NCT04585750) showed that rezatapopt (PC14586) monotherapy produced an overall response rate (ORR) of 46% in patients with platinum-resistant/refractory ovarian cancer harboring a TP53 Y220C mutation, according to a news release from the developer, PMV Pharmaceuticals.¹ The company stated that recent feedback from the FDA continues to support its strategy for submitting a new drug application (NDA) for accelerated approval, which it plans to do in the first quarter of 2027.

What were the updated efficacy results from the PYNNACLE ovarian cancer cohort?

At the May 14, 2026, data cutoff date, the efficacy population comprised 76 patients who had at least 1 post-baseline tumor assessment or discontinued treatment early. Per investigator assessment using RECIST v1.1 criteria, the ORR was 46% (n = 35/76), which included 4 confirmed complete responses, 29 confirmed partial responses, and 2 unconfirmed partial responses. The median time to response was 1.3 months, and the median duration of response was 10.0 months based on confirmed responses only.

The enrollment of patients with platinum-resistant/refractory ovarian cancer for the primary analysis in the phase 2 monotherapy portion of the trial has been completed. The developer plans to update on all PYNNACLE phase 2 pivotal cohorts, including the primary analysis from the ovarian cancer cohort, at a medical conference in the fourth quarter of 2026.

What safety data were reported for rezatapopt in this cohort?

Rezatapopt continued to demonstrate a favorable and consistent safety and tolerability profile across all trial cohorts. Treatment-related adverse events (TRAEs) were mostly grade 1 or 2, and the rate of discontinuation due to TRAEs was 5%. According to the release, the safety and tolerability profile observed in the ovarian cancer cohort was similar to that of the overall PYNNACLE population.

What is the regulatory pathway for rezatapopt in ovarian cancer?

Following a recent meeting with the FDA, PMV Pharma obtained feedback that continues to support its plan to submit an NDA for accelerated approval of rezatapopt in patients with platinum-resistant/refractory ovarian cancer harboring a TP53 Y220C mutation based on data from the phase 2 portion of PYNNACLE. The company anticipates submitting the NDA in the first quarter of 2027.

Rezatapopt previously received fast track designation from the FDA for locally advanced or metastatic solid tumors with a p53 Y220C mutation, along with orphan drug designation for TP53 Y220C–positive ovarian, fallopian tube, and primary peritoneal cancers. Previously reported findings from the PYNNACLE trial showed a 33% ORR across the full solid tumor population and a 43% ORR in the ovarian cancer cohort as of an August 4, 2025, data cutoff.²

What is the PYNNACLE trial evaluating, and how does rezatapopt work?

Rezatapopt is a first-in-class, small molecule p53 reactivator designed to selectively bind the pocket in the p53 Y220C mutant protein, restoring wild-type tumor-suppressor function. The ongoing phase 1/2 PYNNACLE trial is evaluating rezatapopt monotherapy, dosed at 2000 mg once daily, in patients with advanced solid tumors harboring a TP53 Y220C mutation.³ The phase 2 portion is a registrational, single-arm, basket trial comprising 5 cohorts—ovarian, lung, breast, endometrial cancers, and other solid tumors—conducted across approximately 70 sites. The primary objective was evaluating rezatapopt's efficacy at the recommended phase 2 dose.

Eligible patients for the trial were either 18 years or older, or 12 to 17 years after Safety Review Committee approval. They had a locally advanced or metastatic solid malignancy with a TP53 Y220C mutation that was previously treated with 1 or more lines of anticancer therapy and progressive disease, as well as an ECOG performance status of 0 or 1, adequate organ function, and measurable disease.

In the phase 2 monotherapy cohort, the primary end point was ORR per RECIST v 1.1 evaluated by independent review across all cohorts and in the ovarian cohort.

References

1. PMV Pharmaceuticals announces updated promising rezatapopt monotherapy interim ovarian cancer data from PYNNACLE phase 2 pivotal trial. News release. PMV Pharmaceuticals, Inc. August 31, 2026. Accessed September 1, 2026. https://tinyurl.com/2yewchbn
2. PMV Pharmaceuticals announces promising rezatapopt monotherapy interim data from PYNNACLE phase 2 trial across multiple solid tumors with a TP53 Y220C mutation. News release. PMV Pharmaceuticals, Inc. September 10, 2025. Accessed September 1, 2026. https://tinyurl.com/4uxnj92t
3. The evaluation of PC14586 in patients with advanced solid tumors harboring a TP53 Y220C mutation (PYNNACLE). ClinicalTrials.gov. Updated August 10, 2026. Accessed September 1, 2026. https://tinyurl.com/5chshtyk