A new mesothelioma drug controlled the disease in two out of three patients through 12 weeks of treatment. Researchers say it turns cancer’s own defenses against it. Teams at the University of Vermont and University of Leicester led the small, early-phase trial. Their findings were published July 14 in the journal Nature Communications. Key findings from the study show that the drug RSO-021 controlled mesothelioma in six of nine evaluable patients at 12 weeks at the 90-milligram dose. One patient had a partial response, with the tumor shrinking and the response lasting until week 30. The drug is delivered through a catheter already in place for fluid buildup around the lungs, a common mesothelioma symptom. Median progression-free survival was 18 weeks. At 80 weeks, seven of 12 mesothelioma patients were still alive. Side effects of the working dose were mostly mild and no deaths were linked to the drug. This drug should provide additional years to people’s lives.
For years, researchers gave people with mesothelioma and other cancers antioxidants, hoping to lower those damaging molecules and slow tumor growth. Those trials mostly failed. Some even found that added antioxidants helped tumors grow faster. The research team flipped this approach. Instead of protecting cells from oxidative damage, they went after an antioxidant enzyme called PRX3 directly. Block it, and the tumor cell drowns in the very damage it normally holds off. Mesothelioma cells run hot with unstable molecules called reactive oxygen species. Every cell produces some of these as a byproduct of normal metabolism, but cancer cells produce far more. To survive that internal damage, tumor cells lean hard on PRX3, tucked inside their mitochondria, the cell’s energy centers. The drug RSO-021 is derived from a natural antibiotic called thiostrepton. It disables PRX3` permanently once it binds with it. In lab testing, tumor cells with PRX3 removed entirely stopped growing well before drug testing even reached mice. When researchers tried to grow tumors from those same cells in animals, none of them took hold.
Most mesothelioma patients develop fluid buildup between the lung and chest wall, called a pleural effusion, and need a catheter to drain it regularly. Researchers used the same catheter to deliver the drug straight to the tumor, once a week. That approach keeps the dose concentrated where the cancer is, and largely out of the bloodstream. Blood levels of the drug stayed low throughout the trial, barely above what the testing equipment could detect. Levels in the lung fluid told a different story, climbing steadily with each weekly dose until they leveled off. Researchers also tracked how much fluid needed to be drained from patient’s lungs over time. That volume dropped significantly during treatment, from a median of 700 milliliters a week before starting the drug to 175 milliliters a week by the time patients came off treatment.
There were 15 participants in this first-in-human trial, 12 of whom had pleural mesothelioma that had already progressed after standard treatment. Three participants had different cancers that had spread to the lining of the lung. Researchers tested three dose levels: 90, 120, and 180 milligrams. The lowest dose, 90 milligrams, turned out to be the sweet spot. No patients at that dose had serious drug-related side effects. Higher doses caused more problems, including shortness of breath and inflammation severe enough to stop treatment in a few cases. The most common side effects at the working dose were fatigue, mild fever, and cough. Nearly all reported side effects were mild.
RSO-021 is not approved for use outside clinical trials. It remains investigational, and these results come from a small phase 1 study designed primarily to test safety and determine the right dose. Phase 2 has already wrapped, with fuller results expected at a major oncology meeting later this year. Researchers are also working on an oral version of the drug that could eventually make mesothelioma treatment easier to access and could potentially be useful for cancers beyond mesothelioma. Patients interested in emerging mesothelioma treatments can ask their care team whether trials involving RSO-021 are enrolling and whether a pleural catheter they already have could make them a candidate.
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