New research presented by Amplia Therapeutics (ASX:ATX) is drawing attention to a potential strategy that could improve the effectiveness of an emerging class of cancer treatments targeting KRAS mutations, one of the most widely studied drivers of solid tumours worldwide.
At a specialist cancer research conference in Los Angeles, the company shared preclinical data suggesting that its lead drug candidate, narmafotinib, may significantly enhance the activity of KRAS inhibitors across several cancer models.
The findings were presented at the American Association for Cancer Research Special Conference on RAS Oncogenesis and Therapeutics, an event focused on advances in targeting the RAS family of cancer genes. According to Amplia, the results demonstrate that narmafotinib can work alongside KRAS inhibitors to strengthen treatment responses in laboratory models of pancreatic, lung and ovarian cancers.
KRAS mutations are among the most common genetic alterations in cancer and have historically been difficult to target with drugs. In recent years, however, pharmaceutical research has accelerated rapidly in this area. More than fifty KRAS inhibitor drugs are currently being investigated in clinical trials globally, reflecting intense interest in therapies that can block these powerful cancer drivers.
Despite promising progress, KRAS inhibitors face important challenges. Many patients experience significant side effects, and tumours frequently develop resistance to treatment over time. Amplia’s research suggests narmafotinib may help address one of these key problems by blocking cellular pathways that cancers use to escape the effects of KRAS inhibitors.
Narmafotinib works by inhibiting focal adhesion kinase, a protein involved in tumour growth, survival and the development of fibrotic tumour environments. This protein is often overexpressed in aggressive cancers such as pancreatic cancer. By targeting this pathway, narmafotinib appears to interfere with resistance mechanisms that can emerge when KRAS inhibitors are used alone.
In preclinical experiments presented at the conference, the addition of narmafotinib improved tumour growth inhibition in multiple KRAS-driven cancer models. Researchers observed enhanced responses in both tumours already sensitive to KRAS inhibitors and those that were less responsive. The results suggest the combination could potentially improve the durability and depth of treatment responses if confirmed in clinical studies.
Amplia Therapeutics chief executive Dr Chris Burns said the company sees strong potential in combining narmafotinib with the growing range of KRAS-targeted drugs now being developed across the pharmaceutical industry. Presenting the data at a conference dedicated to RAS biology offered an opportunity to discuss collaboration with companies already working in the field.
The company is already advancing narmafotinib through clinical development. The drug is currently being tested in patients with advanced pancreatic cancer in combination with standard chemotherapy regimens. Early results from the ACCENT trial report a confirmed objective response rate of 35 per cent, higher than the benchmark response rate observed with chemotherapy alone in a widely referenced study. Interim results also indicate a median progression-free survival of 7.7 months.
A second clinical trial, known as AMPLICITY, has recently begun enrolling patients in Australia and the United States. This study is evaluating narmafotinib in combination with the chemotherapy regimen FOLFIRINOX for people with advanced pancreatic cancer.