Drug Combined With Immunotherapy “Thwarts Tumor Growth,” Increases Survival

Oncologists report success in some cancer patients treated with immunotherapy. However, researchers continue to search for ways to increase the effectiveness to expand the mesothelioma treatment to even more patients – hopefully, to more mesothelioma patients. Now, a team of researchers report that a combination treatment that blocks a protein while at the same time awakening the immune system could be the next break needed to increase survival in cancer patients.

Read about another study where using a two-pronged approach to improve immunotherapy could help mesothelioma patients.

Researchers at MD Anderson Cancer Center found that patients treated with ipilimumab (Yervoy), an immune checkpoint inhibitor, developed an elevated level of  EZH2, a protein shown to suppress T cell activity. T cells are critical for helping fight cancer, and ipilimumab, a CTLA-4 checkpoint inhibitor, works by creating an immune response by interfering with the action of CTLA-4 on T cells. But, the team found that when the CTLA-4 action is blocked, EZH2 levels increased.

The researchers turned their focus to finding a way to stop the interference of EZH2 on the T cells. This led the team to target both CTLA-4 and EZH2, to inhibit the protein. When the team tested this combination approach in mouse models with bladder cancer and melanoma, they found that combining ipilimumab with a drug that inhibits EZH2 “caused major reductions in tumor growth” and “significantly increased survival.”

“Immune checkpoint therapy has led to significant clinical responses in some patients but in order to provide benefit to even more patients, we will need rationally designed combination therapies,” said senior author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at MD Anderson, in a June 15 press release announcing the findings.

Mesothelioma, a terminal asbestos-caused cancer, and melanoma are both notoriously aggressive and difficult to treat. Both have shown some success with both ipilimumab, from Bristol-Myers Squibb, and Keytruda, an immunotherapy drug from Merck that works by targeting the cellular pathway PD-1/PD-L1. Mavis Nye of England, who is a nine-year mesothelioma survivor, was brought to remission through a clinical trial with Keytruda.

Nearly 3,000 Americans are diagnosed with mesothelioma each year, and many of these die within a year of diagnosis. The mesothelioma community anxiously awaits results of further information about ipilimumab.

MD Anderson has now opened a Phase I clinical trial to test the combination with melanoma and in lung cancer.

Information about the MD Anderson study can be found in the June 15 issue of the Journal of Clinical Investigation.

https://www.jci.org/articles/view/99760

Sources:

• MD Anderson
  https://www.mdanderson.org/newsroom/2018/06/researchers-find-combination-can-enhance-ipilimumab-immunotherapy.html
• Phase I clinical trial
  https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2017-0928.html