Results of a Phase 1B clinical trial presented earlier this week at the 2016 European Lung Cancer Conference in Geneva, Switzerland demonstrate that a new immunotherapy treatment using live bacterium might eventually become a treatment of choice for individuals suffering from malignant pleural mesothelioma.
According to the clinical trial coordinators and study authors, the use of this immunotherapy combined with the standard chemotherapy used to treat pleural mesothelioma patients resulted in more than 90 percent disease control and a 59 percent response rate in patients plagued with this otherwise difficult-to-treat form of cancer, which attacks the lining of the lungs and is caused by exposure to asbestos.
Dr. Thierry Jahan, professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, was pleased with the results. “Standard of care treatment with pemetrexed (Alimta™) and platinum compound chemotherapy gets a 30% response rate but a modest impact on survival. So there is a clear unmet need in targeting this specific population,” he noted.
Scientifically speaking, Jahan explained that patients stricken with malignant pleural mesothelioma strongly express the mesothelin antigen in their tumors. The therapy being tested, known as CRS-207, is a “live, attenuated Listeria monocytogenes bacterium that contains two gene deletions to diminish its pathogenicity and has also been engineered to express mesothelin,” Jahan explained to his fellow doctors and researchers at the convention, which is held annually.
“In our early studies, CRS-207 induced an anti-mesothelin response and cellular tumor specific immunity in patients with mesothelin expressing tumors,” noted Dr. Jahan. “We also have data suggesting that this immunotherapy works synergistically with chemotherapy, so testing the effect of this immune targeting agent with chemotherapy was a natural step.”
The trial included 38 patients who have pleural mesothelioma that could not be treated with surgery. However, they were candidates for chemotherapy and hadn’t yet tried chemo to treat their disease. Each received two infusions of CRS 207, two weeks apart, and up to six cycles of chemotherapy, three weeks apart. At the conclusion of the chemo, they received two more bacterium immunotherapy infusions and then maintenance doses every eight weeks until the time of disease progression.
At median follow-up time, which occurred at about 9.4 months, a startling 59 percent of patients had partial response and 35 percent enjoyed disease stabilization. Those are extremely high percentages for mesothelioma patients, who often pass within a year of their diagnosis.
Jahan also pointed out that there were few side effects associated with the new immunotherapy vaccination. Most patients reported problems with temperature spikes and rigors within a few hours of the infusions, but these disappeared within about 24 hours. In all, the drug was well tolerated, even when combined with the chemotherapy drugs.
A randomized trial with this immunotherapy vaccination is currently in the planning stages, says Jahan, and he hopes it’ll be underway before 2016 is over. That’s good news for the 2,000-3,000 Americans and the thousands of others worldwide who are diagnosed with malignant pleural mesothelioma each year.
To date, these patients have had to deal with debilitating treatments that have been less than successful and prognoses that are almost always grim.