Amplia Therapeutics (ASX: ATX) has halted recruitment in its AMPLICITY trial due to dose-limiting toxicities (DLTs) related to the chemotherapy component, prompting a strategic pivot.
This decision follows the observation of three protocol-defined DLTs among eight patients dosed with narmafotinib in combination with mFOLFIRINOX for advanced pancreatic cancer.
The company clearly stated that these DLTs were not attributed to narmafotinib, but linked to the mFOLFIRINOX chemotherapy regimen, known for its tolerability challenges.
Despite the halt in new recruitment, the five patients already enrolled and still on study will continue their treatment under ongoing safety monitoring.
Strategy Shift to New Combinations
Following the issues with the mFOLFIRINOX combination, Amplia Therapeutics will redirect its resources.
The focus will now shift towards exploring other combination strategies for narmafotinib, moving away from FOLFIRINOX.
This strategic pivot implies a delay in the expansion of the AMPLICITY trial as originally conceived and postpones future readouts for the narmafotinib plus mFOLFIRINOX regimen.
The company anticipates a growing preference for less toxic chemotherapy options in the future.
Early Efficacy Signals Observed
Even with the recruitment pause, Amplia highlighted early efficacy signals from the limited patient cohort in the AMPLICITY trial.
Of the eight patients dosed, four demonstrated stable disease at their first two-month scan.
Notably, one of these four patients also recorded a partial response at the four-month scan.
This is an indication of some positive clinical activity for narmafotinib in this difficult-to-treat cancer.
ACCENT Trial Performance
This shift in strategy comes after positive updates from Amplia’s other key trial, ACCENT.
The ACCENT trial, which combines narmafotinib with gemcitabine/Abraxane in advanced pancreatic cancer, has shown promising results.
Previous data reported a 7.8% confirmed complete response rate among 64 patients in the 400 mg cohort, with a median overall survival of 11.1 months.
These results were described as an improvement compared to historical benchmarks for gemcitabine/Abraxane alone, with no additional toxicity attributed to narmafotinib.
Investor Risks Remain
The recent development in the AMPLICITY trial underscores existing investor risks.
Clinical trial interpretation risks persist, largely due to the single-arm study design of some of Amplia’s trials and the reliance on historical benchmarks for efficacy and survival comparisons.
Furthermore, funding and cash burn remain key dependencies for the company’s continued development.
Amplia’s Half Yearly Report and Accounts for the six months ended 30 September 2025 highlighted an increased net loss and R&D expenses, with future funding contingent on ongoing capital and R&D tax incentive receipts.
