Can Amplia’s Narmafotinib Redefine Pancreatic Cancer Treatment?

Context and Significance

Amplia Therapeutics Limited (ASX – ATX) has unveiled positive interim topline data from its ongoing ACCENT clinical trial, investigating narmafotinib, a novel FAK inhibitor, in combination with standard chemotherapy for advanced pancreatic cancer. This announcement marks a notable development in a field where treatment options remain limited and patient outcomes poor.

Pancreatic cancer is notoriously aggressive, with a five-year survival rate lingering around 3%. Current standard treatments, such as gemcitabine combined with Abraxane or the more intensive FOLFIRINOX regimen, offer median progression-free survival (PFS) of approximately 5.5 to 6.4 months. Amplia’s data suggests that adding narmafotinib may push this boundary further.

Key Trial Outcomes

The ACCENT trial’s interim analysis reveals a median PFS of 7.6 months, representing a two-month improvement over chemotherapy alone and outperforming FOLFIRINOX. The objective response rate (ORR) stands at 31%, compared to 23% in the benchmark MPACT study, while the disease control rate (DCR) is an impressive 73%, significantly higher than the 50% observed historically.

Durability of response is also a highlight, with seven patients remaining on trial beyond 12 months and a mean duration on trial of 202 days, nearly doubling the 117 days seen with chemotherapy alone. Importantly, the safety profile of the narmafotinib combination closely mirrors that of chemotherapy alone, indicating no substantial increase in adverse events or patient burden.

Implications and Next Steps

Amplia’s CEO Dr Chris Burns emphasised the encouraging nature of these results, noting the drug’s potential to improve outcomes without compromising tolerability. The company is accelerating plans to initiate a pivotal Phase 2b/3 trial in the second half of 2026, aiming to confirm these findings in a larger, controlled setting.

Further patient updates from the ACCENT trial are expected in the second half of 2025, with mature data, including overall survival metrics, anticipated in the first quarter of 2026. Additionally, Amplia is preparing to launch a US-based trial combining narmafotinib with FOLFIRINOX, expanding its clinical development footprint.

Broader Context in Oncology

Narmafotinib targets Focal Adhesion Kinase (FAK), a protein implicated in tumour growth, metastasis, and treatment resistance. By inhibiting FAK, Amplia aims to disrupt the tumour microenvironment and enhance the efficacy of existing therapies. This approach aligns with growing interest in targeted therapies that complement chemotherapy and immunotherapy.

While the data is interim and derived from a single-arm, open-label study without a direct comparator arm, the improvements in key efficacy endpoints and tolerability profile provide a compelling rationale for further investigation. The oncology community will be watching closely as Amplia advances narmafotinib through its clinical pipeline.