New Immunotherapy Clinical Trial Targets Common Mesothelioma Protein
February 19, 2019
A biotechnology company specializing in innovative cancer therapeutics has opened a clinical trial examining an immunotherapy drug targeting a protein found in 90 percent of malignant mesothelioma tumors.
It is the first clinical trial to specifically study a patient population characterized by this protein expression.
The target is known as VISTA, a surface protein which inhibits the immune system from working properly and allows the mesothelioma to grow.
The drug is CA-170, an orally available molecule and the only anti-VISTA drug being studied today in a cancer clinical trial.
And the potential could be huge.
“The hope is that by inhibiting VISTA — which is very prominent in mesothelioma — it would inhibit the cancer growth and allow the immune system to attack the cancer better,” Dr. Robert Martell, head of Research and Development at Curis Inc., told The Mesothelioma Center at Asbestos.com. “The goal is that patients will be able to control this cancer.”
Mesothelioma Cohort Part of Larger Study
A larger study of CA-170 — looking at other advanced solid tumors and lymphomas — has been active since 2016, but the drug targets a different protein.
A mesothelioma cohort within the larger study was added only recently. The first patient enrolled earlier this year.
“What we’ve seen so far [with the other cancers] is excellent safety. The drug is well tolerated, with no significant toxicity,” Martell said. “We’ve also seen clear signs of tumor shrinkage. We’ve had a number of patients experience the tumor shrinkage.”
VISTA is unique in that it is expressed in immune cells and in mesothelioma tumor cells, according to Martell.
It has been identified as a potential resistance mechanism, limiting the effectiveness of other treatments that work with some cancers but not with mesothelioma.
CA-170 has shown an ability to inhibit both VISTA and PD-L1, another immune-system inhibitor that has been targeted effectively in other malignancies, including non-small cell lung cancer.
May Help Keytruda Work Better
Earlier research has suggested the presence of VISTA within the mesothelioma tumors is a reason that the immunotherapy drug Keytruda works well for only a small percentage of mesothelioma patients.
The versatility of CA-170 could possibly solve that problem.
“VISTA is so highly expressed in mesothelioma, which suggests that the tumor growth might be dependent on it. And our drug targets VISTA. That’s why we think our drug might have a chance of working well,” he said. “Obviously we don’t know, ultimately, what will happen yet, but the hope is to control the cancer.”
Unfortunately, the search for an effective treatment for mesothelioma has been frustrating the medical community for many years.
Less than 50 percent of those diagnosed with pleural mesothelioma survive more than one year. An estimated 10 percent live five years or more after diagnosis.
The FDA has not approved a new treatment for mesothelioma since 2004 when the chemotherapy combination of Alimta (pemetrexed) and cisplatin became the standard of care.
Various immunotherapy drugs have shown promise — and are working — with other cancers, but mesothelioma patients have not been as fortunate.
Effective treatments have been elusive.
CA-170 is the latest — and potentially the most promising — to move into the clinical trial stage.
Several Cancer Centers Hosting the Trial
Curis is looking initially for only 12 patients. They will be evaluated at two dose levels.
Those who qualify for the trial in the U.S. can enroll at the following sites:
“We have a new therapy that targets a unique aspect of mesothelioma,” Martell said. “That’s encouraging. We have a lot of hope now that we can deliver something new, and helpful, for these patients.”