Aydah AlAwadhi, Consultant Medical Oncologist and Division Chair of Hematology and Oncology Department at Sheikh Shakbout Medical City, shared a post on LinkedIn:
“A Big Milestone in Oncology: Targeting the “Undruggable” p53 – A long awaited proof of principle
Now, a Phase 1 study published in NEJM Group reports promising results with rezatapopt, targeting the TP53 Y220C mutation in advanced solid tumors.
Key highlights from the PYNACLE trial:
- 77 heavily pretreated patients
- 20% overall response rate
- Up to 30% response in KRAS – wild type tumors at higher doses
- Tumor shrinkage across ovarian, breast, lung, prostate, and other cancers
- Mostly mild toxicities (nausea, fatigue)
- Phase 2 trials already underway
Is this the beginning of truly drugging mutant p53?
Too early to declare victory, but this is proof of principle that structure-guided reactivation of mutant p53 is biologically achievable.
Moving forward, molecular selection, co-mutation context (e.g., KRAS), and biomarker-driven trial design will be key.”
Titel: Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C – Mutated Tumors
Authors: Ecaterina E. Dumbrava, Geoffrey I. Shapiro, Aparna R. Parikh, Melissa L. Johnson, Anthony W. Tolcher, John A. Thompson, Anthony B. El-Khoueiry, Andrae L. Vandross, Shivaani Kummar, Dale R. Shepard, Kim LeDuke, Lisa Sheehan, Leila Alland, Arshad Haque, Deepika Jalota, Marc Fellous, and Alison M. Schram.
Read the Article
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