Rezatapopt Shows 46% ORR in TP53 Y220C–Mutated Ovarian Cancer

Rezatapopt (PC14586) demonstrated a 46% objective response rate (ORR) in patients with TP53 Y220C–mutated, platinum-resistant/refractory ovarian cancer, according to a news release.¹

The updated interim data come from the phase 1/2 PYNNACLE trial (NCT04585750), a multicenter, single-arm, registrational study evaluating rezatapopt monotherapy at a dose of 2000 mg once daily in patients with TP53 Y220C–mutated advanced solid tumors. As of a May 14, 2026, data cutoff, rezatapopt produced responses in 35 of 76 patients with TP53 Y220C–mutated ovarian cancer, including 4 confirmed complete responses. PMV Pharmaceuticals plans to provide an update on all PYNNACLE pivotal cohorts at a conference in the fourth quarter of 2026, and has received FDA feedback on the path to submitting a new drug application for accelerated approval of rezatapopt in TP53 Y220C–mutated ovarian cancer in the first quarter of 2027.

PYNNACLE Trial Design and Updated Efficacy Data

PYNNACLE is a global multicohort basket trial assessing rezatapopt, a selective p53 reactivator, across multiple locally advanced or metastatic solid tumors with TP53 Y220C mutations; the primary end point is ORR by blinded independent central review. The PYNNACLE trial's ovarian cancer cohort has completed enrollment; the trial's other cohorts enrolled patients with lung, breast, and endometrial cancers and other solid tumors, totaling approximately 200 patients.

At the data cutoff, 46% of patients in the pivotal ovarian cancer cohort achieved an objective response per investigator assessment using RECIST v1.1, including 4 confirmed complete responses, 29 confirmed partial responses, and 2 unconfirmed partial responses. In the PYNNACLE ovarian cancer cohort, the median time to response to rezatapopt was 1.3 months, and the median duration of response was 10.0 months.

The updated PYNNACLE data build on results presented earlier in 2026 at the Society of Gynecologic Oncology Annual Meeting on Women's Cancer, where rezatapopt produced clinically meaningful activity across ovarian cancer subgroups regardless of platinum refractoriness or resistance, prior therapy, or FRα expression, with an investigator-assessed ORR of 44.4% and a median duration of response of 8.2 months.²As of the March 29, 2026, data cutoff, approximately 40% of patients remained on rezatapopt treatment.

Safety and Tolerability of Rezatapopt

Rezatapopt continued to show a favorable and consistent safety and tolerability profile across all PYNNACLE cohorts, according to the sponsor, with treatment-related adverse effects (TRAEs) that were mostly grade 1 or 2.¹ The rate of treatment discontinuation due to TRAEs was low, at 5%, and the safety and tolerability profile in the ovarian cancer cohort was similar to that of the overall trial population. The most frequent TRAEs previously reported included nausea, fatigue, and increased blood creatinine levels.²

About Rezatapopt: Mechanism and Regulatory Status

Rezatapopt is a first-in-class, small molecule p53 reactivator designed to selectively bind the pocket in the p53 Y220C mutant protein and restore wild-type tumor-suppressor function. The FDA has granted rezatopopt fast track designation for locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation, as well as orphan drug designation for TP53 Y220C–positive ovarian, fallopian tube, and primary peritoneal cancers.¹ The Y220C hotspot mutation occurs in an estimated 3.1% of ovarian cancers and 3.6% of high-grade serous ovarian cancers.²

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 2, 2026. https://tinyurl.com/3zfx5ja7

2. Schram AM, Frenel J-S, Italiano A, et al. The PYNNACLE phase 2 trial assessing rezatapopt, a selective p53 reactivator, in patients with advanced or metastatic solid tumors harboring a TP53 Y220C mutation: interim analysis of patients with ovarian cancer. Presented at: 2026 SGO Annual Meeting on Women's Cancer; April 10-13, 2026; San Juan, PR.