Update from AACR–NCI–EORTC 2025: PYNNACLE Phase 2 evaluating rezatapopt in TP53 Y220C–mutant solid tumours

Drs Alison Schram and Elena Garralda share expert insights on the PYNNACLE Phase 2 initial analysis at AACR–NCI–EORTC 2025. Rezatapopt, a first-in-class p53 reactivator, is evaluated in TP53 Y220C–mutant locally advanced and metastatic 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 

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