PMV Pharma plans to conduct a Phase 1/2 open-label, multicenter study to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of PC14586 in adult patients with a p53 Y220C mutation in locally advanced or metastatic solid tumors. Phase 1 is a first-in-human, open-label, dose-escalation study designed to up to 30 patients with solid tumors that have a p53 Y220C mutation using next-generation sequencing. Phase 2 is an open-label study designed to assess anti-tumor efficacy and safety in patients with solid tumors that have a p53 Y220C mutation. Phase 2 is expected to enroll up to 100 patients.
p53 plays a pivotal role in cellular function by preserving the integrity of DNA and preventing abnormal cells from entering or progressing through the cell cycle. Mutant p53 takes on oncogenic properties that endow cancer cells with a growth advantage and resistance to anti-cancer therapy. Mutant p53 proteins are very common and are found in approximately half of all human cancers. The p53 Y220C mutation is associated with many cancers including but not limited to breast, non-small cell lung cancer, colorectal, pancreatic and ovarian cancers.
PC14586 is a first-in-class, orally available structural corrector of the p53 Y220C mutant protein, designed to selectively bind to the crevice created by the p53 Y220C mutation, hence, restoring the wild-type, or normal, p53 protein structure and tumor suppressing function. PC14586 is being developed for the treatment of patients with locally advanced or metastatic solid tumors that have a p53 Y220C mutation.