Florent Peyraud, Medical Oncologist at Bergonié Institute, posted on LinkedIn:
“A major step forward has just been published in NEJM Group! The PYNNACLE phase 1 study of rezatapopt, a selective p53 Y220C reactivator, demonstrates that restoring wild‑type p53 conformation and activity in tumors carrying this specific mutation is clinically achievable. After KRAS, the era of turning undruggable targets into druggable ones is advancing with TP53.
TP53 mutations are among the most frequent genomic alterations across human cancers and have long been associated with poor outcomes.
In this trial:
- 77 heavily pre‑treated patients with advanced solid tumors harboring TP53 Y220C received rezatapopt,
- 20% ORR was observed, with confirmed responses across multiple tumor types,
- a manageable safety profile, with GI toxicities (i.e. nausea, vomiting) often alleviated when taken with food
- established 2000 mg daily as the RP2D
This represents a significant milestone: a first‑in‑class agent successfully reactivating a mutant p53 allele in patients – a concept that had remained out of reach for decades.
We are pleased and proud that Institut Bergonié is participating as an active recruiting center in this innovative clinical study PMV Pharmaceuticals, Inc.. This trial offers a promising therapeutic option for patients with advanced solid tumors carrying a TP53 Y220C mutation.
To consider a patient for enrolment, molecular profiling of tumor is mandatory. Please refer your patients via the Klineo platform, allowing us to perform screening and evaluate eligibility for innovative treatments available within our early phase program.
Title: Restoring Function to a Variant of p53 in Solid Tumors
Authors: Xin Lu
Other articles featuring Florent Peyraud on OncoDaily.