Amplia uncovers new clue in pancreatic cancer drug trial

Amplia Therapeutics has delivered a sweeping update on its four-front clinical assault with lead drug narmafotinib, targeting some of the toughest cancers, including pancreatic, ovarian and lung cancer. Headlining the progress snapshot is an intriguing new clue from its key pancreatic cancer trial, suggesting the drug’s effectiveness may not depend on whether a patient’s tumour carries certain cancer-driving mutations in the KRAS gene.

KRAS gene mutations are genetic changes that can cause cells to grow and divide uncontrollably, helping drive disease development. The gene normally acts like an on-off switch, controlling signals that tell cells when to grow. When mutated, the switch can become permanently stuck in the “on” position, encouraging cancer cells to multiply.

The finding is significant as pancreatic cancer treatment is rapidly shifting towards targeted therapies. KRAS gene mutations are found in more than 90 per cent of pancreatic cancers, making them a major focus for drug developers.

The US Food and Drug Administration (FDA) recently approved a new KRAS-targeting drug that showed a significant survival benefit, highlighting the potential of this new class of therapies. Amplia’s data, however, suggest its Focal Adhesion Kinase (FAK) inhibitor narmafotinib could work alongside the KRAS drugs, potentially making it effective in a broader patient population or in powerful combination treatments.

‘It is exciting to be moving forward with these trials as the company build on positive clinical data.’

Amplia Therapeutics chief medical officer Dr Jason Lickliter

Narmafotinib works by blocking a protein known as FAK, which is found at unusually high levels in solid tumours such as pancreatic cancer. The protein plays a key role in helping cancer cells grow, survive and resist treatment. FAK also contributes to the creation of dense, scar-like fibrotic tissue that forms a protective fortress around some tumours. By blocking FAK, the company believes narmafotinib can weaken or even break down this biological barrier, giving chemotherapy a cleaner shot at destroying the cancer cells within.

Amplia’s ACCENT trial, which is evaluating narmafotinib combined with standard chemotherapy in newly diagnosed metastatic pancreatic cancer patients, has delivered promising results. Previously reported data showed a significant response rate of 36 per cent, a median overall survival of 11.1 months and a complete response rate of a stunning 7.8 per cent, a figure considered historically rare in pancreatic cancer.

The latest findings suggest the treatment may also have serious staying power, with two patients now having clocked a remarkable two years in the study and a third still receiving treatment after 19 months.

Amplia Therapeutics chief medical officer Dr Jason Lickliter said: “It is exciting to be moving forward with these trials as the company builds on the positive clinical data from the ACCENT trial and the promising preclinical data underpinning the PRROSE and Lilly combination studies.”

While its ACCENT trial continues to deliver, the company has also advanced three other clinical trials into the late-stage start-up phase.

The first, dubbed ACCENT-Mini, is being designed to evaluate a daily dosing regimen of narmafotinib in addition to chemotherapy at three Australian sites. Ethics approval is expected imminently, with safety and pharmacokinetic data anticipated in the first half of 2027. Management says this data will be crucial for its submission to the US FDA for a larger registrational study.

The company is also tackling ovarian cancer with its PRROSE study, opening a second major front for its lead drug. The Australia New Zealand Gynaecological Oncology Group will run the trial in collaboration, sponsoring and coordinating it through its extensive network of more than 1650 members.

Like ACCENT-Mini, the PRROSE trial will pair narmafotinib with established chemotherapy drugs, this time carboplatin and paclitaxel, targeting women with high-grade serous ovarian cancer who have shown a limited response to their initial treatment.

The main goals are to assess the combination’s safety and explore whether it can increase the proportion of patients eligible for successful surgical resection. With the trial protocol finalised and ethics approval submitted, Amplia is nearing recruitment of 26 patients across Australia and New Zealand.

Rounding out the pipeline, the company is preparing a separate update on its trial combining narmafotinib with global pharmaceutical giant Lilly’s experimental KRAS G12C inhibitor, olomorasib. The study will target patients with advanced non-small cell lung cancer, exploring the potential of attacking the disease on multiple fronts by combining drugs that target different cancer-driving pathways. Amplia believes blocking the FAK protein could help shut down a pathway cancer cells use to resist KRAS-targeted treatments.

With four trials pushing ahead across a range of hard-to-treat cancers, Amplia appears to be methodically building a case for its cancer drug narmafotinib. The suggestion that its lead drug could work independently of the KRAS mutations that dominate pancreatic cancer might just be the key to unlocking its potential as a standalone or combination therapy in a field crying out for new options.

Is your ASX-listed company doing something interesting? Contact: mattbirney@bullsnbears.com.au