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Another immunotherapy failure

[newdaydawning]

Incyte-Merck trial failure deals a blow to cancer immunotherapy, but researchers remain hopeful

• Incyte's new immunotherapy drug epacadostat failed to work in conjunction with Merck's blockbuster melanoma drug Keytruda.
• Only a small group of patients react to immunotherapy, and cancer researchers argue this study took too broad of a sample.
• The field of immunotherapy needs more research and may still offer value to patients. 

Rick Morgan| @RickAnselMorgan

The future of cancer immunotherapy looks promising, but it suffered a major setback on Friday. Incyte announced that its trial drug epacadostat did not help melanoma patients, and the company is halting the study altogether.

Epacadostat was supposed to work in conjunction with Merck's blockbuster cancer immunotherapy drug Keytruda — which has delivered billions in revenue to the pharmaceutical giant — to help the immune system fight cancer. The immune system contains T cells. These cells know the difference between a normal cell they should leave alone and a foreign cell they should attack. The problem is many cancer cells also look normal to T cells. Keytruda helps T cells recognize and fight cancer cells. Drugs like Keytruda are called "checkpoint inhibitors."

Epacadostat was supposed to further immunotherapy. The body contains an enzyme called IDO, which stops T cells from doing their job. Epacadostat is an IDO inhibitor, meaning it stops IDO from suppressing T cells.
 

Incyte hoped epacadostat, in conjunction with Keytruda, would fight cancer more effectively than Keytruda alone. But epacadostat failed to stop the progression of cancer, and it hasn't helped overall survival. The disappointing trial caused Incyte stock to drop more than 19 percent on Friday; Merck shares were down near 3 percent, though that merely matched the selloff in the stock market.

"We are disappointed that this study did not confirm the efficacy of epacadostat in combination with KEYTRUDA in patients with unresectable or metastatic melanoma," said Dr. Steven Stein, chief medical officer of Incyte, in a release. "We remain dedicated to transforming the treatment of cancer and will continue to explore how IDO1 inhibition and other novel mechanisms can potentially improve outcomes for patients in need."

After halting the melanoma study, Incyte wants to test epacadostat with other types of cancer. Dr. Jason Luke, an oncologist at the University of Chicago, believes the Incyte study examined a patient sample that was too broad. Only patients with T cell-inflamed tumors react to immunotherapy at all. Patients without T cell-inflamed tumors don't have a natural immune response against cancer. IDO inhibitors won't make any difference.

"This is why we need to select those patient that have an immune response," said Luke. For patients that have the natural immune response, epacadostat still might be effective. Unfortunately, this is the minority of cancer patients.

Doctors can use RNA-based sequencing to test if a patient would be a prime candidate for immunotherapy. Although the Incyte and Merck press release mentions lung cancer, Luke said IDO inhibitors might help this minority of patients with any type of cancer.

Dr. Roy Herbst, a Yale University oncologist, believes there is no one-size-fits-all cancer solution. "You have to personalize immunotherapy," he said. "You need to know who will benefit from drug A and who will benefit from drug B."

The more research that goes into immunotherapy, the more doctors will understand how best to treat patients. Combining different medications, like Merck and Incyte were trying to do, could improve treatment in the future.

 

Even with the trial failure, "That's all the interest right now," Herbst said.

The future of cancer immunotherapy looks promising, but it suffered a major setback on Friday. Incyte announced that its trial drug epacadostat did not help melanoma patients, and the company is halting the study altogether.

Epacadostat was supposed to work in conjunction with Merck's blockbuster cancer immunotherapy drug Keytruda — which has delivered billions in revenue to the pharmaceutical giant — to help the immune system fight cancer. The immune system contains T cells. These cells know the difference between a normal cell they should leave alone and a foreign cell they should attack. The problem is many cancer cells also look normal to T cells. Keytruda helps T cells recognize and fight cancer cells. Drugs like Keytruda are called "checkpoint inhibitors."

Epacadostat was supposed to further immunotherapy. The body contains an enzyme called IDO, which stops T cells from doing their job. Epacadostat is an IDO inhibitor, meaning it stops IDO from suppressing T cells.
 

Incyte hoped epacadostat, in conjunction with Keytruda, would fight cancer more effectively than Keytruda alone. But epacadostat failed to stop the progression of cancer, and it hasn't helped overall survival. The disappointing trial caused Incyte stock to drop more than 19 percent on Friday; Merck shares were down near 3 percent, though that merely matched the selloff in the stock market.

"We are disappointed that this study did not confirm the efficacy of epacadostat in combination with KEYTRUDA in patients with unresectable or metastatic melanoma," said Dr. Steven Stein, chief medical officer of Incyte, in a release. "We remain dedicated to transforming the treatment of cancer and will continue to explore how IDO1 inhibition and other novel mechanisms can potentially improve outcomes for patients in need."

After halting the melanoma study, Incyte wants to test epacadostat with other types of cancer. Dr. Jason Luke, an oncologist at the University of Chicago, believes the Incyte study examined a patient sample that was too broad. Only patients with T cell-inflamed tumors react to immunotherapy at all. Patients without T cell-inflamed tumors don't have a natural immune response against cancer. IDO inhibitors won't make any difference.

"This is why we need to select those patient that have an immune response," said Luke. For patients that have the natural immune response, epacadostat still might be effective. Unfortunately, this is the minority of cancer patients.

Doctors can use RNA-based sequencing to test if a patient would be a prime candidate for immunotherapy. Although the Incyte and Merck press release mentions lung cancer, Luke said IDO inhibitors might help this minority of patients with any type of cancer.

Dr. Roy Herbst, a Yale University oncologist, believes there is no one-size-fits-all cancer solution. "You have to personalize immunotherapy," he said. "You need to know who will benefit from drug A and who will benefit from drug B."

The more research that goes into immunotherapy, the more doctors will understand how best to treat patients. Combining different medications, like Merck and Incyte were trying to do, could improve treatment in the future.

 

Even with the trial failure, "That's all the interest right now," Herbst said.

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