Rezatapopt Shows Activity in Pretreated Ovarian Cancer With TP53 Mutation

Rezatapopt, an investigational targeted therapy, led to tumor shrinkage and lasting responses in patients with advanced ovarian cancer whose tumors carry a TP53 Y220C mutation, according to findings presented at the 2026 SGO Annual Meeting on Women’s Cancer. The treatment appeared to work even in patients whose disease had already been treated with multiple prior therapies, including those with treatment-resistant cancer.

According to study author Dr. Alison M. Schram, a gynecologic medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, these findings suggest that rezatapopt may offer a new treatment approach for this specific group of patients.

How effective is rezatapopt in ovarian cancer?

In the phase 2 PYNNACLE trial, 44.4% of patients experienced tumor shrinkage, also called an overall response rate. This included 1.4% of patients whose cancer was no longer detectable and 43.1% who had partial tumor shrinkage. An additional 31.9% of patients had stable disease, meaning their cancer did not grow, while 6.9% experienced disease progression.

Responses to treatment occurred quickly, with a median time to response of 1.3 months. The median duration of response was 8.2 months, meaning many patients maintained their response for several months. At the time of the analysis, about 40% of patients remained on treatment.

What is rezatapopt and how does it work?

Rezatapopt is a first-in-class oral therapy designed to target the TP53 Y220C mutation. This mutation affects the p53 protein, which normally helps control cell growth and prevent tumors. When mutated, the protein loses its ability to suppress cancer.

This drug works by restoring the normal shape and function of the mutated p53 protein, helping it regain its tumor-fighting ability. The TP53 Y220C mutation is found in approximately 3.1% of ovarian cancers and about 3.6% of high-grade serous ovarian cancers.

Who was included in the PYNNACLE trial?

The PYNNACLE trial is a global phase 2 study evaluating rezatapopt in patients with advanced or metastatic cancers that have the TP53 Y220C mutation. This analysis focused on the ovarian cancer group.

Patients enrolled were heavily pretreated, with a median of four prior lines of therapy. The median age was 66 years. Most patients had difficult-to-treat disease, including those whose cancer was resistant or refractory to platinum-based chemotherapy. Additionally, 80% of patients had previously received bevacizumab, and some had been treated with PARP inhibitors.

Patients received rezatapopt as a once-daily oral treatment.

Does rezatapopt work across different patient groups?

Rezatapopt showed similar levels of effectiveness across multiple patient subgroups, including those with treatment-resistant disease and those previously treated with other therapies. Response rates remained consistent regardless of platinum sensitivity, prior use of bevacizumab or PARP inhibitors, or folate receptor alpha (FRα) expression. These findings suggest the treatment may be effective for a broad range of patients with this specific mutation.

What side effects were seen with rezatapopt?

Side effects were generally manageable and mostly mild to moderate. The most common side effects included nausea, fatigue, and increased creatinine levels, which is a lab value related to kidney function. Other side effects included anemia, increased liver enzymes, vomiting, decreased appetite, diarrhea, and itching.

Most side effects were temporary and could be monitored or managed. No treatment-related deaths were reported, and about 5% of patients stopped treatment due to side effects.

Does rezatapopt target the TP53 mutation effectively?

Researchers also measured circulating tumor DNA to better understand how the drug was working in the body. Among patients with available data, 95% experienced a reduction in the TP53 mutation signal after starting treatment. Many patients had large reductions, with 85% showing at least a 50% decrease and 60% showing a reduction of at least 90%.

These findings support that rezatapopt is successfully targeting the TP53 Y220C mutation and may be helping drive the tumor responses seen in patients. Schram noted in the presentation that the drug may represent a promising, chemotherapy-free oral treatment option for patients with this mutation, although more research is needed. For patients, this means rezatapopt could potentially offer another option in the future, especially for those whose cancer has stopped responding to standard treatments.

References

1. Schram AM, Frenel J-S, Italiano A, et al. The PYNNACLE phase 2 trial assessing rezatapopt 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.
2. PYNNACLE Clinical Study. PMV Pharmaceuticals, Inc. October 2025. Accessed April 12, 2026.

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