Amplia Therapeutics Advances Narmafotinib with Phase 2b Daily Dosing Trial in Pancreatic Cancer

New Dosing Regimen Targets Enhanced Therapeutic Potential

Amplia Therapeutics (ASX:ATX) has kicked off a Phase 2b study to test a daily dosing schedule of narmafotinib, its lead FAK inhibitor, in combination with standard chemotherapy for advanced pancreatic cancer. This marks a strategic pivot from the intermittent dosing used in earlier trials, aiming to build on the encouraging efficacy signals seen in the Phase 1b/2a ACCENT study. CEO Dr Chris Burns highlighted that the prior intermittent schedule showed no significant tolerability issues and delivered promising survival outcomes, fueling confidence that daily dosing could unlock even greater benefits.

The study will enroll 12 patients across 3-4 Australian sites, split evenly between two dosing cohorts. Each cohort will receive narmafotinib alongside gemcitabine and Abraxane, administered on their conventional schedules. Key endpoints include safety, tolerability, pharmacokinetics, and exploratory biomarker analyses focusing on fibrosis; a hallmark of FAK activity. Patient recruitment is slated to begin in Q4 2026, with initial safety and PK data expected by mid-2027.

Regulatory Alignment and Resource Redeployment Accelerate Progress

This Phase 2b trial is designed in close consultation with the US FDA, serving as the first stage of a planned registrational Phase 3 study. Amplia has leveraged drug product and resources from the wind-down of its AMPLICITY trial, which investigated narmafotinib with FOLFIRINOX but was halted due to chemotherapy toxicity concerns. This redeployment has enabled an accelerated start to the new trial phase without delay. The company believes incorporating this daily dosing data will strengthen its upcoming FDA submission.

These developments follow Amplia’s recent disclosure of mature ACCENT trial results, which reported a 36% objective response rate and median overall survival of 11.1 months; outcomes that outpace chemotherapy alone. The ACCENT data also included multiple complete responses and demonstrated no additional toxicity with narmafotinib, underscoring its potential as a best-in-class FAK inhibitor in pancreatic cancer. The company’s manufacturing scale-up and positive regulatory feedback on dosing optimisation further underpin this clinical momentum.

Clinical and Commercial Implications for a Challenging Indication

Pancreatic cancer remains one of the most lethal malignancies, with limited effective treatment options and poor prognosis. Amplia’s focus on FAK inhibition addresses a critical unmet need, targeting tumour fibrosis and the tumour microenvironment to potentially improve chemotherapy response. The incorporation of biomarker endpoints in this Phase 2b trial could provide valuable insights into narmafotinib’s mechanism and patient stratification.

While the trial’s small initial cohort size means early data will be preliminary, the design reflects a cautious but strategic approach to dose optimisation ahead of larger pivotal studies. Amplia is also advancing narmafotinib in other indications, including ovarian cancer, where it recently launched the PRROSE trial targeting resistant disease, highlighting the drug’s broader potential.