FDA Grants Fast Track to Novel Small Molecule for Locally Advanced or Metastatic Solid Tumors

The FDA has granted a Fast Track designation to the novel agent PC14586 for the treatment of patients with locally advanced or metastatic solid tumors that harbor a P53 Y220C mutation, PMV Pharmaceuticals, Inc., announced in a press release.

At this time, there are no FDA-approved treatments available that target the P53 Y220C mutation, which is associated with many cancers, including breast, non–small cell lung, colorectal, pancreatic, and ovarian cancers.

“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 David Mack, PhD, president and chief executive officer of PMV Pharma, in a statement.

P53 is known to play a vital role in the cell function by preserving the integrity of DNA and preventing abnormal cells from entering/progressing through the cell cycle. The mutation has oncogenic properties endowing cancer cells with a growth advantage and resistance to anti-cancer therapy. P53 mutations are common, occurring in approximately half of all cancers.

PC14586 is a first-in-class small molecule that has been designed to structurally correct the P53 Y220C mutation. The company plans to initiate a phase 1/2 clinical trial (NCT04585750) to evaluate the safety and activity of this treatment.

The open-label, multicenter study will assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of PC14586 as treatment of adult patients with P53 Y220C-mutant locally advanced or metastatic solid tumors. The phase 1 is a first-in-human, dose-escalation study that has been designed for up to 30 patients. The phase 2 is designed to assess the anti-tumor efficacy and safety of the drug in patients with solid tumors that harbor a P53 Y220C mutation, which is expected to enroll up to 100 patients.

“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,” stated Mack.

The primary end points of the phase 1 will be the safety and maximum tolerated dose, and clinical activity/safety in the phase 2. Secondary end points include clinical activity/efficacy in the phase 1 and pharmacokinetics of PC14586 and metabolites in both phases.

To be included in the study, patients must have an advanced solid malignancy with a P53 Y220C mutation, an ECOG performance status of 0 or 1, prior treatment with at least 1 line of anticancer therapy and progressive disease, and adequate organ function. They had to be at least 18 years old or aged 12 to 17 years after adequate adult safety data become available.

Patients will be excluded from enrollment if they received an anti-cancer therapy within 21 days of receiving the study drug, radiotherapy within 28 days, had primary central nervous system tumor, a history of leptomeningeal disease or spinal cord compression, or brain metastases, unless it’s asymptomatic and does not require steroids for at least 2 weeks prior to receiving the study drug. If the patient has had a stroke or transient ischemic attack within 6 months of screening, heart conditions, or a history of gastrointestinal disease that could interfere with the absorption of a study drug, they are excluded from enrollment to the study.

_References

_{PMV Pharma Granted FDA Fast Track Designation of PC14586 for the Treatment of Advanced Cancer Patients that have Tumors with a p53 Y220C Mutation. News Release. PMV Pharmaceuticals. October 13, 2020. Accessed October 14, 2020. https://yhoo.it/3jZ9MQT}