Immunotoxin SS1P Proving Effective Against Mesothelioma
July 16, 2014
Medical oncologist Raffit Hassan, M.D., has studied SS1P, the genetically engineered immunotoxin, for more than 15 years, believing it could become the key to therapeutic advancements for malignant pleural mesothelioma.
He is getting closer to finding it.
In Hassan’s latest clinical trial at the National Cancer Institute, SS1P was particularly effective when used in combination with the pemetrexed/cisplatin chemotherapy regimen that has become the standard, first-line treatment for cancer patients.
The Phase I study, which began in 2011 and is still ongoing, was designed to determine the maximum tolerated dose (MTD) of SS1P, and to see just how effective it would be when used in conjunction with the chemo combination. SS1P helped significantly.
Researchers define partial response as at least a 30-percent reduction in total tumor development. Progressive disease is defined as an increase of at least 20 percent of total tumor measurement. Stable is when neither the criteria for progressive disease nor partial response are met.
Of the 13 patients who received the MTD along with the chemotherapy, 10 showed at least a partial, positive response and tumor shrinkage. Only two saw their disease continue to progress. One reported stable disease.
The result was considerably better than the typical response with chemotherapy alone, which has been inconsistent at best in helping mesothelioma patients.
“SS1P given with pemetrexed and cisplatin is safe and well-tolerated and exhibits significant antitumor activity in patients with unresectable, advanced pleural mesothelioma,” Hassan’s wrote in his conclusion.
Tumor Reduction Is Possible
Hassan’s original trial included 24 patients at four dose levels, but four of them were unable to be evaluated for a variety of reasons. Of the 20 who tested, 12 of them (60 percent) had at least partial response, three had stable disease and five had progressive disease.
SS1P works because it contains an antibody that attaches to a specific protein on mesothelioma cells. It also contains a toxin that can enter and kill the cells, but only if the antibody attachment is successful.
Unlocking the vast potential of SS1P has been one of Hassan’s goals for years, as it has been for other researchers at NCI. Last fall Hassan detailed some of his earlier clinical work with SS1P at the World Conference on Lung Cancer in Sydney, Australia.
Researchers at NCI discovered that SS1P worked well with a pentostatin/cyclophosphamide drug combination designed as an immune suppressor, killing mesothelioma cells without harming healthy ones.
It was part of a clinical trial involving patients with advanced, unresectable mesothelioma. One patient had a 74 percent tumor reduction that was maintained through the next 15 months.
“We believe this was pretty significant. Everyone was pleasantly surprised,” Hassan told Asbestos.com when detailing the findings.
Patients Can Explore SS1P Clinical Trial
SS1P by itself was not as effective in treating mesothelioma because patients would naturally develop antibodies to the immunotoxins, reducing their effectiveness. The drug combination allowed SS1P to work more efficiently, which has led to more follow-up research.
The latest SS1P research was done in conjunction with the University of Chicago Medical Center. The SS1P trial involving the chemotherapy combination is no longer recruiting new patients at the NCI, but the one with the pentostatin/cyclophosphamide combination continues to accept participants.