Amplia launches Phase 2b narmafotinib trial in pancreatic cancer

Amplia Therapeutics has initiated a Phase 2b study of narmafotinib in advanced pancreatic cancer, exploring a daily dosing regimen in combination with gemcitabine and Abraxane. The Melbourne-based company said the study has been designed in alignment with FDA feedback and is intended to form the first stage of a registration-enabling Phase 3 programme.

The trial will recruit 12 patients across two dosing cohorts — six patients per cohort — at three to four Australian sites. Safety, tolerability, pharmacokinetics, and efficacy will all be assessed, with exploratory endpoints including effects on disease biomarkers and fibrosis markers as indicators of focal adhesion kinase (FAK) activity. Patient enrolment is expected to begin by the fourth quarter of 2026, with safety and pharmacokinetic data from all 12 patients anticipated by the second quarter of 2027.

Building on earlier data

Amplia says the Phase 2b design builds directly on results from its earlier ACCENT Phase 1b/2a study, in which narmafotinib combined with gemcitabine and Abraxane produced a response rate of 36% and a median overall survival of 11.1 months in first-line advanced pancreatic cancer patients — figures the company characterises as superior to chemotherapy alone. Narmafotinib holds both orphan drug and fast track designations from the FDA for this indication.

The current programme also benefits from resources freed up by the wind-down of recruitment in the AMPLICITY trial, which had been investigating narmafotinib alongside FOLFIRINOX. Chief executive Chris Burns said prior studies used only an intermittent dosing schedule, and that moving to daily dosing "may further enhance the therapeutic potential of narmafotinib." He added that the company believes inclusion of Phase 2b data will strengthen its eventual registrational submission to the FDA.

Market and competitive context

Pancreatic cancer remains one of oncology's most intractable indications, with gemcitabine/Abraxane and FOLFIRINOX the established first-line backbones for advanced disease and five-year survival rates still below 15%. The high unmet need has drawn a range of investigational approaches, including KRAS-targeted therapies, PARP inhibitors for BRCA-mutant subgroups, and stromal-targeting strategies. FAK inhibition occupies the stromal-remodelling space: FAK is overexpressed in pancreatic tumours and is thought to contribute to the dense fibrotic microenvironment that limits drug penetration and immune infiltration, making it a mechanistically plausible target.

Amplia is not alone in pursuing FAK in solid tumours — several academic groups and a small number of other companies have explored FAK inhibition, though the competitive field has thinned in recent years as earlier inhibitors showed limited single-agent activity. Narmafotinib's combination approach and the relatively clean tolerability profile reported from ACCENT may differentiate it, but investors will be watching the forthcoming 12-patient safety and PK readout closely before drawing conclusions about the daily-dosing hypothesis. The company's ASX listing and small cohort sizes reflect the capital-efficient, milestone-driven model typical of Australian clinical-stage biotechs navigating the path to a US registration filing.