Cancer Drug Targeting Rare Mutation Works Across Tumor Types

(Bloomberg) -- Finding single therapies that can treat tumors based on their genetics rather than their location in the body has been a longstanding goal of medical research. A new drug may bring that a step closer to reality for a small group of patients.

An experimental cancer medication made by Loxo Oncology Inc. helped shrink a variety of tumors caused by a rare genetic anomaly in more than three out of every four patients who received it in a small clinical trial.

The study of 55 patients found that after treatment with Loxo's larotrectinib, 12 percent of people whose tumors who could be assessed had no sign of cancer, while 64 percent showed partial shrinkage of their tumors. The disease was stable in 12 percent of patients and got worse in 12 percent.

Rare Mutation

Loxo's drug targets a mutation where two genes join together in what's known as TRK fusion, leading to the production of proteins that cause cancer growth. It's rare -- about 1 percent of cancers have the anomaly, and it's seen in 1,500 to 5,000 patients annually in the U.S., according to Loxo Chief Executive Officer Josh Bilenker.

“In many ways, this represents the original promise of precision medicine, where your tumor's genetics determines whether you respond to therapy,” said lead researcher David Hyman, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York.

“I hope this raises the ambition of the field to go after targets without concern for their frequency,” Hyman said. “There is no cancer that is too rare to go after as long as the drug works.”

The study simultaneously measured the drug's effectiveness in both children and adults, a first in the development of a cancer drug, and encompassed 17 different types of cancer, Hyman said.

The results were presented at the American Society of Clinical Oncology's annual meeting in Chicago on Saturday. Loxo, based in Stamford, Connecticut, funded the study.

The patients had advanced, aggressive cancers that responded almost immediately to the treatment, Hyman said. Many were feeling better within days of receiving the drug and showed a response by the time they underwent their first imaging scan, after less than two months.

“It was not subtle, what was happening in the study,” Hyman said, mentioning one patient who had a mass in his jaw quickly shrink, his pain ebb and spasms calm. “That hasn't been the exception; it's been the rule” for most patients, he said. “This is likely to represent the new standard of care” in patients with the abnormality.

Seeking Approval

Loxo plans to file for U.S. Food and Drug Administration approval of larotrectinib, which was given breakthrough designation a year ago for patients with no other treatment alternatives. An independent laboratory will review the study results before the company submits the drug for U.S. approval, the company said in a statement. That is expected by the end of the year.

If approved, larotrectinib would be the second drug, after Merck & Co.'s Keytruda, cleared for treating cancer based on a tumor's genetic makeup. Keytruda, widely used to get the immune system involved in killing melanoma and other cancers, won accelerated FDA approval in May for advanced cancer based on a biological characteristic rather than where in the body the tumor originated.

The drug, which entered human testing in 2014, is Loxo's most advanced product and would be its first on the market if approved. The company developed the medicine alone and is starting to hire the employees needed to launch it, said Bilenker. Loxo, which has a market value of about $1.28 billion, has seen its shares rise about 53 percent this year to date.

Loxo is working on other compounds, including a follow-on drug for patients who develop resistance to larotrectinib, Bilenker said. The company could look to partner or sell itself to get the treatment to more patients, but it isn't doing that now, he said.

The shift toward genetic-based cancer drugs means more screening is needed to identify patients who may benefit, Bilenker said. Currently only about 10 percent of cancer patients have access to comprehensive genomic profiling, he said.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net.

To contact the editors responsible for this story: Drew Armstrong at darmstrong17@bloomberg.net, Timothy Annett