Update From AACR-NCI-EORTC: PYNNACLE phase 2 study

Drs Alison Schram and Elena Garralda share expert insights on the PYNNACLE Phase 2 initial analysis at AACR–NCI–EORTC 2025.

The PYNNACLE phase 2 study evaluates rezatapopt, a first-in-class p53 reactivator, as a treatment for TP53 Y220C–mutant advanced solid tumours.

In this video, the experts discuss:

• TP53 Y220C mutation and the rationale for mutant p53 reactivation
• Study overview and practice implications, spotlighting ovarian cancer
• Testing strategies for early and accurate patient identification

*Rezatapopt is an investigational agent which is not approved by a regulatory agency

Visit the COR2ED website to learn more and download the accompanying slides and poster for more information here: https://cor2ed.com/n-connect/programm...


Clinical takeaways:

• Reactivating p53 Y220C protein is a promising therapeutic strategy for patients with solid tumours specifically ovarian cancer, with TP53 Y220C mutations, where effective targeted therapies and biomarkers are limited.

• Rezatapopt is a first-in-class investigational p53 reactivator that selectively binds to the mutated p53 Y220C protein, stabilising its structure to restore wild-type tumour suppressor activity.

• Rezatapopt demonstrates rapid, durable and broad antitumour activity in TP53 Y220C–mutant solid tumours, with a particularly strong signal in ovarian cancer, and a generally manageable safety profile.

• Looking ahead, it will be important to prioritise early and accurate identification through up-front comprehensive genomic profiling using NGS with TP53 gene coverage. Tissue is preferred; when tissue is limited, selected ctDNA assays capable of excluding CHIP may be used.


This programme has been sponsored by PMV Pharma

Published October 2025