Amplia Therapeutics' narmafotinib, a Focal Adhesion Kinase (FAK) inhibitor, has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of advanced pancreatic cancer. This designation aims to accelerate the development and review of drugs that show promise in treating serious conditions where current therapies fall short. The company's ACCENT trial is currently underway in Australia and South Korea, with plans to expand to the United States.
Significance of Fast Track Designation
Fast Track Designation is reserved for drugs that demonstrate the potential to offer a significant advantage over existing treatments for serious conditions. It provides Amplia Therapeutics with opportunities for more frequent meetings and written communication with the FDA, potentially leading to Accelerated Approval and Priority Review for narmafotinib. Narmafotinib had previously been granted Orphan Drug Designation by the FDA for pancreatic cancer.
Dr. Chris Burns, CEO and Managing Director of Amplia Therapeutics, stated, "Fast Track Designation for narmafotinib is a significant milestone for the Company. With this designation, we can work more closely with the FDA to accelerate our clinical program and gather the most compelling evidence for regulatory approval in this devastating disease."
Narmafotinib: A FAK Inhibitor
Narmafotinib (AMP945) is a selective inhibitor of FAK, a protein that is often over-expressed in pancreatic and other cancers. FAK is gaining increasing attention as a drug target due to its role in solid tumors. Preclinical studies have shown promising data for narmafotinib, and the drug has successfully completed a healthy volunteer study.
ACCENT Trial Details
The ACCENT trial (NCT05355298) is an open-label Phase 2a trial evaluating the safety, tolerability, and efficacy of narmafotinib in combination with gemcitabine and Abraxane® in patients with pancreatic cancer. Interim analysis of the trial, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that narmafotinib was generally safe and well-tolerated. In the trial, 14 patients elected to continue narmafotinib following their first 28-day cycle, and nine remained on the therapy for five months or longer. Partial responses were confirmed in six patients, with four receiving a 400-mg dose and two receiving a 200-mg dose. One patient experienced a dose-limiting toxicity of grade 3 nausea at the 400-mg dose.
The trial employs a 3+3 design to determine the recommended phase 2 dose (RP2D), with narmafotinib dose escalation of 100 mg, 200 mg, and 400 mg. Based on the Phase 1 data, 400 mg was selected as the RP2D for narmafotinib.
The primary endpoints of the trial include treatment-emergent adverse effects and overall response rate per RECIST v1.1 criteria. Secondary endpoints include plasma concentration of narmafotinib, duration of response, overall survival, progression-free survival, time to progression, and clinical benefit rate.
Pancreatic Cancer Landscape
Pancreatic cancer is a highly aggressive disease with limited treatment options. It is the eighth most commonly diagnosed cancer in Australia, with approximately 1 in 70 individuals expected to be diagnosed by age 85. Current treatments include surgery, endoscopic treatment, chemotherapy, and radiation therapy, often in combination. The Fast Track Designation for narmafotinib represents a significant step forward in the development of new therapies for this challenging disease.
