The new drug developed acts as a potential therapy for RET-driven cancers like medullary and papillary thyroid cancer, non-small cell lung cancer, colorectal and bile duct cancer.
All the above-mentioned cancers were historically difficult to treat.
‘The new drug called BLU-667 acts as a potential therapy for RET-driven cancers such as medullary and papillary thyroid, colorectal and bile duct cancer, and non-small cell lung cancer.’
BLU-667 is an oral drug
that is being investigated in a multicenter, open-label trial.
The pre-clinical and early clinical validation were published online in the issue of Cancer Discovery.
The results of this phase-I trial were presented at the American Association for Cancer Research Annual Meeting 2018, Chicago.
"There is a critical un-met need for effective drugs against cancers that have the RET alteration, as there are no highly potent inhibitors currently approved specifically for these RET-driven cancers," said Vivek Subbiah, M.D., Assistant professor of Investigational Cancer Therapeutics.
Currently, for these cancers, the treatments available are:
- Traditional chemotherapy
- Earlier generations of multiple kinase inhibitors
These treatment methods were hardly successful, as they often gave rise to various side effects and decreased the patient's quality of life.
Subbiah and his team have investigated BLU-667 as a novel precision-targeted drug. Throughout the proof-of-concept trial, the drug was found to show promising activity and disease control, as a highly selective RET inhibitor.
The novel drug, BLU-667 targets RET-altered cancers with fewer side effects that are affecting non-cancerous organs. RET was found to be associated with:
- Half of all medullary thyroid cancers
- Around 20 percent of papillary thyroid cancers and
- About 1 to 2 percent of non-small cell lung cancers
In this study, the research team followed about 43 patients who had advanced tumors and who were not eligible for surgery.
Also, about 26 patients who had medullary thyroid cancer, 15 patients who had non-small cell lung cancer and two patients with other RET-driven cancers were also studied by the research team.
How Effective is BLU-667 Drug?
Subbiah said that in most patients, they had noticed a reduction in tumor and durable responses, especially in those patients whose cancer has progressed with chemotherapy and multi-kinase inhibitors.
In this study, an overall response rate (ORR) of 32 percent for medullary thyroid, with 37 percent for RET-driven cancers, and 45 percent for non-small cell lung cancer have been reported.
The BLU-667 drug was chosen by the research team for investigation, as it is 100 times more selective for RET-driven cancers than other kinases that were tested.
It was found to be effective in stopping genetic mutations, otherwise known as gatekeepers, which have been tied to resistance to multiple kinase therapies.
Subbiah finally concluded saying, "Overall, the data show the precision-targeted therapy with next-generation kinase inhibitors can have a powerful impact on patients with RET-driven cancers. We hope this new therapy will enable patients to benefit from the recent advances in genomic profiling that have revolutionized treatment options for patients with kinase-driven diseases."