FDA Places PC14586, for Cancers with Mutant Protein, on Fast Track

FDA Places PC14586, for Cancers with Mutant Protein, on Fast Track

The U.S. Food and Drug Administration (FDA) has granted fast track designation to PC14586 as a potential treatment of advanced cancers that harbor a specific mutation affecting the protein p53, which includes some ovarian cancers.

Fast track is given to support therapies with the potential to fill a serious unmet medical need. They are eligible for benefits that include more frequent discussions with the FDA, and can be considered for accelerated approval and priority review.

“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,” David Mack, PhD, president and CEO of PMV Pharma, which is developing the therapy, said in a press release.

“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,” added Mack.

PC14586 is designed to target a mutated form of the p53 protein that enables cancer cells to grow out of control.

In non-cancerous cells, the p53 protein acts as a regulator of cell division. Put simply, p53 is part of a mechanism that stops cells from dividing when conditions aren’t optimal — for example, when there is damage to their DNA.

However, in about half of all cancers, the gene that encodes p53 becomes mutated, such that the protein cannot work as it should. The lack of a regulator allows the cell to divide uncontrollably, the hallmark feature of cancer.

One of the more common inactivating mutations in p53 is Y220C, which refers to a substitution of the amino acid tyrosine (Y) at the 220th position in the protein chain, where there is normally a cysteine (C). This change causes the protein to become unstable, ultimately impairing its function.

Currently, there are no FDA-approved medicines that target the p53 Y220C mutation. In addition to ovarian cancer, this mutation is found in breast, colorectal, pancreatic, and non-small cell lung cancers.

PC14586 is an orally available small molecule designed to stabilize the mutant protein, restoring its ability to work.

“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,” said Mack.

PMV is planning evaluate PC14586 in an upcoming Phase 1/2 trial involving 130 people with locally advanced or metastatic solid tumors that harbor a p53 Y220C mutation.

The open-label, multicenter study will be conducted in two parts. In Phase 1, 30 participants will receive ascending doses of this therapy to assess its safety, tolerability, and pharmacokinetics (the movement of a drug into, through, and out of the body).

That part will also establish the optimal dose to be given in Phase 2, which expects to enroll 100 patients to continue studying PC14586’s safety and its anti-tumor activity.