Mesothelioma is a rare and extremely aggressive form of cancer that affects the lining around the lungs, heart and abdominal cavity. It is caused by exposure to asbestos, but symptoms often remain dormant for years or decades. It is difficult to treat and has a five-year survival rate of only 9%, according to the Mesothelioma and Asbestos Awareness Center. Recently, a new clinical trial has begun enrolling and treating mesothelioma patients with an experimental immunotherapy drug called CA-170 in hopes of improving the prognosis.
The current study is a Phase I, open-label dose-escalation and dose-expansion trial that is focusing on studying the safety and initial clinical efficacy of CA-170 in patients. Two dosages are being tested on study participants.
CA-170 is a dual inhibitor of the VISTA protein and the PDL1 protein receptor and is currently the only anti-VISTA therapy being studied. The VISTA protein is present in 90% of mesothelioma tumors and helps cancer cells avoid attack from the immune system. High levels of VISTA expression have also been noted in other cancers, including ovarian, endometrial and non-small cell lung cancer. This suggests that the results from this study could have broader impact if CA-170 proves effective against the VISTA protein.
The PDL1 receptor also stops the immune system from attacking a cancer cell. By stopping both the VISTA and PDL1 communications to the immune system that the cell shouldn’t be attacked, the immune system is able to recognize the cancerous cells and begins attacking the diseased cells.
There are several PDL1 inhibitors currently on the market, including Tecentriq and Imfinzi, which have shown promise in treating mesothelioma. Researchers hope that by combining these effects with a drug that is able to also inhibit the VISTA protein, they will be able to better treat mesothelioma tumors.
The mesothelioma cohort is actually a sub-section of a larger study that has been active since 2016. Other groups in the study are being observed for how CA-170 affects advanced solid tumors and lymphomas, but they focus on a different protein. So far, the drug has shown promising results, as it has been well tolerated with no significant toxicity, as well as preliminary signs of tumor shrinkage.
The Food and Drug Administration has not approved a new treatment for mesothelioma since 2004, when a combination of the chemotherapies, Alimta and cisplatin, became the standard treatment of choice.