New drug effective against several cancers in early trial

By Allen Cone  |  April 16, 2018 at 11:32 AM
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April 16 (UPI) -- A Phase I clinical trial of an investigational drug has shown to be effective and safe for patients with thyroid and non-small cell lung cancers.

Researchers at the University of Texas MD Anderson Cancer Center in Houston have been testing an oral drug, BLU-667, that treats cancers caused by an alteration in the receptor tyrosine kinase known as RET. Their findings were published Monday in the journal Cancer Discovery and presented at the American Association for Cancer Research Annual Meeting 2018 in 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," Dr. Vivek Subbiah, an assistant professor of investigational cancer therapeutics at MD Anderson, said in a press release. "The current treatments for these cancers are limited to traditional chemotherapy and earlier generations of multiple kinase inhibitors. These options have had limited success with often considerable side effects that significantly impact the patient's quality of life."

The authors noted that RET is linked to 50 percent of medullary thyroid cancers, 20 percent of papillary thyroid cancers and 1 percent to 2 percent of non-small cell lung cancers.

In the study, 43 patients with advanced tumors not eligible for surgery were examined along with 26 patients with medullary thyroid cancer, 15 with non-small cell lung cancer and two with other RET-driven cancers.

"Tumor reductions and durable responses were observed in most patients, especially those patients whose cancer progressed with chemotherapy and multi-kinase inhibitors," Subbiah said.

The successful response rate overall was 37 percent for RET-driven cancers, including 45 percent for non-small cell lung cancer and 32 percent for medullary thyroid.

"In vitro, BLU-667 demonstrated 10-fold increased potency over approved multi-kinase inhibitors against oncogenic RET variants and resistance mutants," the researchers wrote.

BLU-667 is 100 times more selective for RET than other kinases tested, the researchers said. The drug has shown it can be effective at stopping genetic mutations, which are known as gatekeepers and have been resistant to multiple kinase therapy.

The drug also has fewer side effects affecting non-cancerous organs.

"Overall, the data show the precision targeted therapy with next-generation kinase inhibitors can have a powerful impact for patients with RET-driven cancers," Subbiah said. "By offering a highly selective medicine tailored for this oncogenic driver, 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."

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