Amplia Therapeutics has released a broad update on its clinical program for lead drug narmafotinib, headlined by a new clue from its key pancreatic cancer trial suggesting the drug's effectiveness may not depend on whether a patient's tumour carries KRAS gene mutations, which are found in more than 90 per cent of pancreatic cancers.
Amplia Therapeutics has delivered a sweeping update on its four-front clinical program with lead drug narmafotinib, which targets some of the hardest-to-treat cancers, including pancreatic, ovarian and lung cancer.
Headlining the update is a finding from its ACCENT trial in newly diagnosed metastatic pancreatic cancer. Previously reported data showed a 36 per cent response rate, a median overall survival of 11.1 months and a complete response rate of 7.8 per cent, a figure the company describes as historically rare in pancreatic cancer. Two patients have now remained in the study for two years, with a third still receiving treatment after 19 months.
The new data suggests the drug's effectiveness may not depend on KRAS mutation status. KRAS mutations act like a switch stuck in the "on" position, driving cancer cells to multiply. The finding matters because pancreatic cancer treatment is shifting toward targeted therapies, and the US Food and Drug Administration recently approved a KRAS-targeting drug that showed a significant survival benefit.
Amplia's data suggest its Focal Adhesion Kinase (FAK) inhibitor could work alongside KRAS drugs, potentially broadening the patient population or enabling powerful combination treatments. Narmafotinib blocks FAK, a protein found at unusually high levels in solid tumours. FAK helps cancer cells grow, survive and resist treatment, and contributes to the dense, scar-like tissue that forms a protective fortress around some tumours. The company believes blocking FAK can weaken or break down that barrier, giving chemotherapy a cleaner shot at the cancer cells.
Beyond ACCENT, Amplia is advancing three other trials into the late-stage start-up phase. ACCENT-Mini will evaluate a daily dosing regimen of narmafotinib plus chemotherapy at three Australian sites, with ethics approval expected imminently and safety and pharmacokinetic data anticipated in the first half of 2027. The company says this data will be crucial for its submission to the US FDA for a larger registrational study.
The PRROSE trial, run with the Australia New Zealand Gynaecological Oncology Group, will pair narmafotinib with carboplatin and paclitaxel in women with high-grade serous ovarian cancer who responded poorly to initial treatment. Amplia is nearing recruitment of 26 patients across Australia and New Zealand.
The company is also preparing an update on a trial combining narmafotinib with pharmaceutical giant Lilly's experimental KRAS G12C inhibitor, olomorasib, in advanced non-small cell lung cancer. Amplia believes blocking FAK could shut down a pathway cancer cells use to resist KRAS-targeted treatments.
Dr Jason Lickliter, Amplia's chief medical officer, 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."
Analysis
Why This Matters
- Pancreatic cancer is among the most difficult cancers to treat, and KRAS mutations are present in more than 90 per cent of cases, making them a major focus for drug developers.
- Amplia's data suggest narmafotinib may work independently of KRAS mutation status, potentially expanding the pool of patients who could benefit and opening the door to combination therapies.
- The company is running four trials at once, positioning itself in a field that has seen recent regulatory momentum with a newly approved KRAS-targeting drug.
Background
KRAS is a gene that 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. Targeted therapies against KRAS have become a major focus of pancreatic cancer research.
Narmafotinib takes a different approach. It blocks FAK, a protein found at unusually high levels in solid tumours. FAK helps cancer cells grow, survive and resist treatment, and contributes to the scar-like fibrotic tissue that forms a protective barrier around some tumours. Amplia's theory is that blocking FAK can break down that barrier and also shut down resistance pathways that cancer cells use against KRAS-targeted drugs.
The ACCENT trial is evaluating narmafotinib combined with standard chemotherapy in newly diagnosed metastatic pancreatic cancer patients. The latest findings point to durability, with several patients remaining on treatment well beyond a year.
Key Perspectives
Amplia Therapeutics: The company is building a case that narmafotinib could work as a standalone or combination therapy. Its chief medical officer describes the progress as exciting, and the company is pushing ahead with four trials designed to generate the data needed for regulatory submission.
Regulators and clinicians: The path to approval runs through the US FDA. Amplia says data from ACCENT-Mini, expected in the first half of 2027, will be crucial to its submission for a larger registrational study. Independent bodies such as the Australia New Zealand Gynaecological Oncology Group are also involved in running trials, adding a layer of external coordination.
Skeptics: As with any early-stage cancer trial, the findings will need to be confirmed in larger, more rigorous studies before regulators approve the drug. Response rates and survival figures from initial cohorts can change as trials expand and longer follow-up data emerge.
What to Watch
- Ethics approval and the start of recruitment for ACCENT-Mini at three Australian sites, with safety and pharmacokinetic data expected in the first half of 2027.
- Recruitment of 26 patients for the PRROSE ovarian cancer trial across Australia and New Zealand.
- The separate update on the Lilly combination study in advanced non-small cell lung cancer.
