New targeted therapy promises strong response rate across 17 cancer types
Loxo Oncology’s lead therapy larotrectinib made a big impact at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, with its latest trial results showing that it could be the first targeted, oral, tumour-type agnostic treatment able to produce benefits across 17 different varieties of cancer and in any patient age.
Larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) fusion proteins, which are caused by a fusion of a TRK gene within a cancer cell and one other gene variety. This occurrence is rare, present only within under 1% of common cancers; however, it is very prevalent within rare cancer types such as salivary gland cancer and infantile fibrosarcoma, being present in over 90% of such cases.
“TRK fusions are rare, but occur in many different cancer types. In fact, at this point it is hard to find a cancer type where TRK fusions have not been reported,” said lead study author David Hyman, Chief of Early Drug Development at Memorial Sloan Kettering Cancer Center in New York. “These findings embody the original promise of precision oncology: treating a patient based on the type of mutation, regardless of where the cancer originated. We believe that the dramatic response of tumours with TRK fusions to larotrectinib supports widespread genetic testing in patients with advanced cancer to see if they have this abnormality.”
Three ongoing Phase 1 and 2 trials examined 55 participants with TRK fusions – 43 of which were adults, and 12 were children – with 17 different types of locally advanced or metastatic cancer, including lung, colon, pancreatic, thyroid, gastrointestinal and melanoma and sarcomas.
When studying the first 50 patients who had been taking part in the trial long enough to have been given at least two scans, it was found that 38 (76%) of them responded to larotrectinib, with 79% of this group remaining progression-free after 12 months. Three patients with paediatric sarcomas which could not be treated with surgery even saw their tumours shrink to a point where they were potentially curable through surgery.
The team now hopes to aim for regulatory approval for the treatment, as Hyman notes: “This dataset, subject to independent central radiology review, will be submitted to FDA for larotrectinib’s regulatory approval. If approved, larotrectinib could become the first therapy of any kind to be developed and approved simultaneously in adults and children, and the first targeted therapy to be indicated for a molecular definition of cancer that spans all traditionally-defined types of tumours.”
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