FDA grants Fast Track Designation to PMV Pharma’s PC14586 for tumors with p53 Y220C mutation

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.

Moleculin reports additional positive interim results from ph 1 trial glioblastoma

Walter Klemp, Chairman and CEO of Moleculin, stated, “The trial in adults has been important in leading the way to establishing a safe and tolerable human dose level for what we believe is a first-in-class compound that crosses the blood-brain barrier and is being developed for the treatment of central nervous system malignancies.  In animal models, WP1066 has been shown to stimulate immune responses that successfully modulate oncogenic transcriptional activity in tumor cells and repress their ability to drive tumor growth.”

According to Mr. Klemp: “In addition to providing valuable pharmacokinetic data, this trial also creates the foundation for future studies in WP1066, including another investigator-initiated study, which is currently being proposed to examine the combination of WP1066 with radiation for the treatment of GBM.  This next clinical trial is being proposed as a result of recent discoveries presented in a peer-reviewed article published in Clinical Cancer Research (Clin Cancer Res June 30 2020 DOI:10.1158/1078-0432.CCR-19-4092), which reported findings that Moleculin’s STAT3 inhibitor, WP1066, used in combination with traditional whole brain radiation therapy, resulted in long-term survivors and enhanced median survival time relative to monotherapy in mice with implanted human brain tumors.”