The Phase IIa ACCENT trial has launched to explore the activity of focal adhesion kinase (FAK) inhibitor narmafotinib in combination with standard-of-care chemotherapy in advanced pancreatic cancer patients.
In November 2023, Amplia Therapeutics announced completion of the Phase Ib stage of the ACCENT trial where ascending doses of narmafotinib, in combination with the standard-of-care chemotherapy regime of gemcitabine and Abraxane, were dosed to first-line patients with advanced pancreatic cancer.
This dose-escalation stage identified a safe and well-tolerated dose of narmafotinib that provides sufficient circulating drug levels to significantly block the activity of the FAK enzyme. Importantly, there were promising preliminary signs of efficacy from the collected Phase Ib data.
The Phase IIa trial is being conducted at six trial sites in Melbourne, Sydney and Brisbane in Australia and five additional sites in Korea. The trial will initially enrol 26 patients and an interim analysis of efficacy will then be conducted in mid-2024.
An efficacy assessment showing six or more partial or complete responses out of the 26 patients will be considered statistically significant to continue the trial. An additional 24 patients will then be enrolled to give a total of 50 patients for this trial.
Amplia CEO and MD Dr Chris Burns commented: “Initiation of the Phase IIa stage of the trial is a significant milestone for Amplia. We are excited to be moving ahead with the next stage of the ACCENT trial with a safe and well-tolerated dose of narmafotinib. The trial in advanced pancreatic patients will determine whether narmafotinib, in combination with gemcitabine and Abraxane, provides improved efficacy for the treatment of this devastating cancer. Patients and clinicians are desperate for improved treatment options given the current five-year survival for newly diagnosed patients is only 12%.”
Pancreatic cancer clinical trial in the US approved
In addition, the US Food and Drug Administration (FDA) has cleared Amplia’s Investigational New Drug (IND) Application for a clinical trial investigating the combination of narmafotinib and FOLFIRINOX in advanced pancreatic cancer patients in the USA.
FOLFIRINOX is a four drug chemotherapy regimen that is widely employed in the US for the treatment of pancreatic cancer.
Burns added: “Clearance of the IND by the US FDA is a significant step forward for the company. We will now start planning the combination trial of narmafotinib with FOLFIRINOX in the US, which expands the clinical opportunities for our best-in-class FAK inhibitor. FOLFIRINOX is the preferred treatment for pancreatic patients in the USA and most of Europe, and therefore this combination trial is highly relevant as we position narmafotinib as the preferred drug to enhance the effectiveness of existing chemotherapy combinations in pancreatic cancer.”
The news follows the announcement by BPGbio that in a Phase IIa clinical trial, its drug BPM31510 doubled the median progression free survival in patients with advanced pancreatic cancers versus gemcitabine alone.