The U.S. Food and Drug Administration (FDA) has granted fast track status to PC14586, PMV Pharmaceuticals’ lead therapeutic candidate for the treatment of patients with locally advanced or metastatic solid tumors, including breast cancer, who have a specific mutation in the gene that encodes the tumor suppressor protein p53.
A fast track designation facilitates the development of potential treatments that cater to unmet medical needs in serious conditions. Medication candidates receiving such status may be eligible for certain benefits, including more frequent interactions with the FDA, and may qualify for priority review, which can speed regulatory approvals.
Currently, there are no FDA-approved treatments that target this specific mutation, called Y220C, in the p53 protein gene.
This designation also is expected to support the launch of an upcoming Phase 1/2 clinical trial, called PMV-586-101 (NCT04585750), which will investigate the safety, tolerability, pharmacological properties, and anti-tumor activity of PC14586 in adults with advanced solid tumors carrying the p53 Y220C mutation. The study, which is not yet recruiting participants, is expected to start later this year.
“Fast Track designation reflects the recognition by the FDA that PC14586 has the potential to address a significant unmet medical need for advanced cancer patients with a p53 Y220C mutation,” David Mack, PhD, president and CEO of PMV Pharma, said in a press release.
“While targeted therapies have improved outcomes for many patients with advanced cancers, those with tumors carrying a p53 mutation do not yet have precision treatment options for these mutations and often have poor outcomes. We look forward to working closely with the FDA as we advance PC14586 through the clinic as part of our mission to discover and develop novel, tumor-agnostic, precision oncology therapies,” Mack said.
The protein p53 is considered a tumor suppressor due to its ability to control cell division rates to prevent excessive cell growth and tumor formation. It does this by directly interacting with DNA and blocking cell division in abnormal cells.
Research has uncovered that one mutation in the gene that encodes p53, called Y220C, is associated with at least 30 different types of cancer, including breast, colorectal, pancreatic, ovarian, and non-small cell lung cancers. Y220C is the ninth-most-frequent p53 mutation, and accounts for 1.8% of all known p53 mutations.
This amino acid swap causes a structural change in the p53 protein, creating a crevice on the protein’s surface that limits its ability to interact with DNA and other molecules. PC14586 is a small molecule that is designed to correct this structural change by filling in the crevice in the protein’s surface, and restoring its tumor suppressor activity.
The upcoming Phase 1/2 trial, planned by PMV Pharma to assess the therapeutic potential of PC14586 in patients with advanced solid tumors, will include two parts.
The first phase of the trial, which will be the first test of PC14586 in humans, will enroll up to 30 individuals with solid tumors carrying the p53 Y220C mutation, verified by advanced DNA sequencing. During this portion of the trial, participants will receive increasing doses of the therapy to determine the maximum tolerated dose, as well as the recommended dose for future testing.
That recommended dose will then be given to those participating in the second phase of the trial, which is designed to evaluate the safety and efficacy of PC14586 in up to 100 patients with solid tumors and the p53 Y220C mutation.
PMV Pharma is focused on developing specific treatments that target p53 mutations. The company was co-founded by Arnold Levine, PhD, who, along with colleagues, discovered the p53 protein in 1979.