Amplia Therapeutics has entered into a clinical trial collaboration and supply agreement with Eli Lilly to evaluate whether its investigational FAK inhibitor narmafotinib can improve treatment outcomes when combined with Lilly’s next-generation KRAS G12C inhibitor olomorasib.
The Phase 1b/2b study will assess the safety and efficacy of the combination as a second-line treatment for patients with advanced non-small cell lung cancer. Amplia plans to conduct the trial at sites in Australia and the United States, with the study expected to begin in late 2026.
Amplia and Lilly had already worked together to prepare an advanced draft of the clinical study protocol before signing the agreement. The companies will now collaborate on finalising the protocol and other documents needed for the trial.
Dr Chris Burns, Amplia’s chief executive officer and managing director, said the agreement marked an important step in the development of narmafotinib.
“This collaboration is an exciting new stage in the clinical progression of narmafotinib. We and others have shown that the combination of FAK and KRAS inhibition can lead to improved outcomes, and we are excited to advance with this clinical study to explore the combination potential with olomorasib, Lilly’s leading KRAS G12C inhibitor currently undergoing two global Phase 3 studies in NSCLC.”
The collaboration expands narmafotinib’s development beyond pancreatic and ovarian cancer and into non-small cell lung cancer, one of the largest markets in oncology. The market is currently valued at approximately US$31 billion and is estimated to exceed US$60 billion by 2032. KRAS G12C mutations are found in about 13 per cent of non-small cell lung cancer cases and between 1 and 3 per cent of other solid tumours.
For Amplia, the agreement also provides a capital-efficient way to pursue the new program. Lilly will supply olomorasib in kind, allowing Amplia to advance the study while using narmafotinib’s expanding clinical evidence base.
Narmafotinib is already being evaluated in the ACCENT trial for advanced pancreatic cancer, where it is used with gemcitabine and nab paclitaxel. Amplia has reported a response rate of 36 per cent, a median overall survival of 11.1 months and a complete response rate of 7.8 per cent in the trial. The company is also conducting the AMPLICITY trial, which combines narmafotinib with mFOLFIRINOX in advanced pancreatic cancer, while recruitment for the PRROSE ovarian cancer trial is scheduled to begin later this year.
The scientific rationale for the new study centres on the challenge of resistance to KRAS G12C inhibitors. Although approved medicines such as sotorasib and adagrasib have improved treatment for patients with KRAS G12C mutant non-small cell lung cancer, their benefits as single agents are often short-lived. Response rates remain modest, and many patients develop resistance within several months.
Researchers increasingly believe that Focal Adhesion Kinase, or FAK, plays a central role in this resistance. When KRAS G12C is inhibited, adaptive activation of FAK can help tumour cells survive and continue proliferating. FAK may also contribute to resistance through YAP signalling, fibrogenesis and changes to the tumour microenvironment.
The planned trial will therefore combine olomorasib’s targeted activity against KRAS G12C with narmafotinib’s potential to suppress resistance pathways driven by FAK. Olomorasib has demonstrated encouraging efficacy and safety results in clinical studies to date and is now being advanced by Lilly in two global Phase 3 registration trials in non-small cell lung cancer.
Amplia is developing narmafotinib as a selective FAK inhibitor for cancer and fibrosis. The company is focused particularly on fibrotic cancers such as pancreatic and ovarian cancer, while also exploring the broader role of FAK in solid tumours and chronic diseases including idiopathic pulmonary fibrosis.
