Rezatapopt in TP53 Y220C mutated metastatic breast cancer: PYNNACLE phase 1/2 update

In this conference update video, Prof. Frédérique Penault-Llorca and Dr Ecaterina Dumbrava provide expert insights into the findings of the PYNNACLE phase 1/2 study presented at SABCS 2024 poster session. This study investigates rezatapopt as a monotherapy for patients with locally advanced or metastatic solid tumours harbouring a TP53 Y220C mutation, including those with metastatic breast cancer (mBC).

The experts discuss:

• The role of TP53 mutations in breast cancer and the significance of the TP53 Y220C variant
• Efficacy and safety results of rezatapopt in patients with mBC harbouring the TP53 Y220C mutation
• The importance of genomic testing for identifying the TP53 Y220C mutation
• Potential implications for clinical practice and future perspectives

Clinical takeaways

• Reactivating wild-type p53 is a promising therapeutic strategy for breast cancers with TP53 mutations, particularly in TNBC, where effective targeted therapies and biomarkers are limited
• Rezatapopt (PC14586) 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
• In a subgroup analysis of the Phase 1 portion of the PYNNACLE trial, rezatapopt demonstrated encouraging preliminary efficacy and safety as a single agent in heavily pre-treated patients with advanced breast cancer harbouring the TP53 Y220C mutation
• Genomic testing is crucial to identify patients with TP53 Y220C mutations who may benefit from this novel treatment approach with rezatapopt

Rezatapopt is an investigational agent which is not approved by a regulatory agency. The Phase 2 portion of the clinical trial is actively enrolling globally.