Amplia Therapeutics Limited (ASX: ATX) has successfully completed the Phase 1b stage of the ongoing ACCENT clinical trial in first- line patients with advanced pancreatic cancer. A safe and well tolerated dose of narmafotinib, the company’s lead asset and best-in-class FAK inhibitor, will now be taken into the Phase 2a portion of the trial that will start imminently.
The Phase 1b stage of the ACCENT trial was designed to test ascending doses of orally-dosed narmafotinib in patients, in combination with the standard-of-care chemotherapy regime of gemcitabine combined with Abraxane. This dose-escalation stage has identified a dose of narmafotinib that provides sufficient circulating drug levels to significantly block the activity of the FAK enzyme. Importantly, this dose has been shown to be safe and well-tolerated across the three cohorts of patients (14 in total) in the trial.
The Phase 1b study was not powered for an efficacy readout, however, all patients were assessed for the impact drug treatment had on their cancer using the international standard Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The initial data obtained for the first 14 patients who completed the trial as per protocol, whilst preliminary and in some cases requiring a confirmatory scan, are positive, with 36% of patients demonstrating a partial response as their best overall response, and with a disease control rate (combined partial response and stable disease) of 93%. These numbers compare very favourably with the published data of the clinical benefit of the gemcitabine and Abraxane combination in pancreatic cancer. Across all doses, narmafotinib was shown to be generally safe and well-tolerated. All patients who completed their first 28-day cycle of treatment elected to stay on narmafotinib, with 7 patients (as of 27th October) having received narmafotinib as part of the combination for 5 months or more. As previously reported, one dose-limiting toxicity event was observed and notably, no treatment-related adverse events greater than Grade 3 were considered related to narmafotinib.
The clinical trial data has been reviewed by the ACCENT Safety Review Committee who support the dose selection and moving to the Phase 2a (Part B) stage of the trial. The Phase 2a trial will be run at the seven trial sites open in Melbourne, Sydney and Brisbane, with five additional sites in Korea expected to open by the end of this year.
Amplia’s CEO and Managing Director Dr Chris Burns commented: “Completion of the Phase 1b stage of the trial is an important milestone for the ACCENT trial. We have now identified a safe and well- tolerated dose of narmafotinib to take into the Phase 2a stage of the trial and the preliminary efficacy signals we have seen to date, across three dose cohorts, are very encouraging. The team at Amplia are now focused on executing the next phase of the trial as quickly and efficiently as possible. As always, we thank the patients for participating in the trial, and the clinical trial staff and investigators for their continued involvement in the trial.”
