Mali Barbi, Medical Oncologist at Northwell Health, shared a post on X:
“Not every breakthrough at SGOAM 2026 is an ADC.
Rezatapopt is a small molecule that does something we thought was impossible – it drugs mutant p53.
TP53 Y220C creates a destabilizing pocket in the protein. Rezatapopt binds it, stabilizes the mutant p53 back into wildtype conformation, and restores transcriptional function. Oral. Once daily.
No chemo. PYNNACLE phase 2 interim in 72 platinum-resistant TP53 Y220C-positive ovarian cancer patients: ORR 44.4%, median DoR 8.2 months, only 5.3% discontinued due to toxicity.
Responses held across prior PARPi, prior bevacizumab, FRα-positive and negative. Heavily pretreated. Didn’t matter.
The ctDNA story seals it. 95% of patients with available data had reductions in TP53 Y220C VAF at 3-6 weeks. 85% dropped 50% or more.
VAF decline tracked radiographic response. That is on-target proof of mechanism in humans.
One practical point: eligibility requires TP53 Y220C specifically – not just TP53 mutated. Make sure your NGS reports are flagging it.”
Other articles about Ovarian Cancer on OncoDaily.
