An experimental drug that uses mesothelioma’s response to cellular stress against it showed early signs of activity in a small phase 1 clinical trial.
The drug, called RSO-021, is designed to block an enzyme that helps mesothelioma cells survive. Researchers reported that six of nine evaluable patients with previously treated pleural mesothelioma had stable or reduced tumors after 12 weeks.
The results are encouraging because the participants had already experienced disease progression following systemic treatment. However, RSO-021 remains investigational, and the trial was too small to establish whether it helps patients live longer than currently available treatments.
RSO-021 is an experimental treatment developed by RS Oncology. It contains a formulated version of thiostrepton, a naturally occurring compound that can interfere with a protein called peroxiredoxin 3, or PRX3. PRX3 is an antioxidant enzyme found inside mitochondria, which are structures that produce much of the energy cells need to function.
As cancer cells grow and process energy, they produce unstable molecules called reactive oxygen species. These molecules can damage cells when their levels become too high. Mesothelioma cells may already contain unusually high levels of reactive oxygen species. To survive, the cells rely on antioxidant defenses such as PRX3 to control the damage. RSO-021 is designed to block PRX3. Researchers hope this allows reactive oxygen species to accumulate until the resulting stress damages or kills the mesothelioma cells. In simple terms, the treatment attempts to disable one of the systems mesothelioma cells use to protect themselves.
Researchers used gene-editing technology to remove PRX3 from human mesothelioma cells. Without the enzyme, the cells produced less energy, divided more slowly, and lost much of their ability to form colonies. The altered mesothelioma cells also failed to produce detectable tumors when implanted into mice. Control cells that continued producing PRX3 formed tumors.
Researchers separately tested thiostrepton on tumor samples collected from 22 patients with mesothelioma. The treatment triggered cancer cell death in some samples, although the response varied.
These experiments supported the idea that PRX3 could be a potential mesothelioma treatment target. They also showed that not every tumor may respond equally well.
The MITOPE study is a phase 1/2 clinical trial evaluating RSO-021 in patients with advanced cancers affecting the pleura, including pleural mesothelioma.
The published phase 1 portion included 15 participants:
All 12 mesothelioma patients had the epithelioid cell type, a malignant pleural effusion, and previous disease progression following systemic treatment.
A malignant pleural effusion is a buildup of fluid between the lung and chest wall caused by cancer. It can contribute to shortness of breath, chest discomfort, and other symptoms.
Participants needed an indwelling pleural catheter to enter the trial. This is a small tube placed in the chest to drain excess fluid. Researchers used the same catheter to administer RSO-021 directly into the pleural space once a week. Local delivery allowed the drug to reach the area around the tumor while limiting the amount circulating through the rest of the body. Treatment continued until medical imaging showed that the cancer had progressed.
The phase 1 trial primarily evaluated safety and tolerability and identified a dose for further research. It was not designed to prove that RSO-021 works better than another mesothelioma treatment.
Researchers selected 90 milligrams as the dose for further study. None of the seven participants treated at this level experienced a dose-limiting side effect. Higher doses caused more serious reactions. Two of six participants treated with 120 milligrams experienced dose-limiting effects, including an acute inflammatory reaction and shortness of breath. One of two participants receiving 180 milligrams experienced severe shortness of breath.
The most commonly reported treatment-related health problems included:
Almost all reported side effects were considered mild or moderate. The published study did not identify any treatment-related deaths.
Tests found very little thiostrepton in participants’ blood after treatment. Higher concentrations remained in the pleural fluid, suggesting that local administration may limit exposure elsewhere in the body.
The study reported a 67% disease-control rate at 12 weeks. This does not mean tumors disappeared in 67% of patients.
Nine mesothelioma patients could be evaluated at 12 weeks:
Together, the partial response and five cases of stable disease produced a disease-control rate of six out of nine patients, or 67%.
Among all 10 evaluable trial participants across the different cancer types, one experienced a partial response. That patient’s tumor reduction continued through week 30 and reached a maximum measured decrease of approximately 61%. The amount of fluid drained from the chest also decreased during the study. Among the available samples, median weekly drainage fell from 700 milliliters before treatment to 175 milliliters when treatment ended. However, the researchers noted that pleural fluid commonly decreases after an indwelling pleural catheter is placed. The study therefore does not show that RSO-021 caused the reduction in fluid or improved symptoms related to pleural effusion.
Median progression-free survival among nine assessable patients with mesothelioma was 18 weeks, or approximately 4.2 months. Progression-free survival measures how long patients live without their cancer growing or spreading. It does not necessarily mean a treatment extends a patient’s life.
Median overall survival had not been reached when researchers analyzed the data at 80 weeks. Seven of the 12 mesothelioma patients were alive at that point.
This finding deserves additional study. However, the trial included only 12 patients with mesothelioma and did not have a control group receiving another treatment. Researchers therefore cannot determine from this study whether RSO-021 caused patients to live longer than they would have with another therapy.
The laboratory portion of the research identified several genetic characteristics that may affect how mesothelioma cells respond to PRX3 inhibition.
Tumor samples with alterations involving the BAP1 and SETD2 genes appeared more sensitive to thiostrepton in laboratory testing. However, the study did not establish either alteration as a proven clinical biomarker for RSO-021. Researchers also found evidence that increased activity of a protein called SLC7A11 may help mesothelioma cells resist treatment. Blocking SLC7A11 made thiostrepton more effective against mesothelioma cells in laboratory experiments.
These findings may eventually help researchers identify which patients are most likely to benefit or develop drug combinations that overcome resistance. More research involving patients is needed before mesothelioma doctors can use these genetic findings to guide care.
Many mesothelioma clinical trials investigate new forms of chemotherapy, immunotherapy, or medications targeting specific genetic alterations. RSO-021 takes a different approach by targeting the system cancer cells use to manage oxidative stress.
The delivery method is also unusual. Administering the drug directly into the pleural space may expose tumors to a higher concentration while reducing exposure elsewhere in the body.
The phase 1 findings show that researchers were able to:
These findings provide a reason to continue studying RSO-021. They do not demonstrate that it should become part of standard mesothelioma treatment.
The phase 1 trial included only 12 patients with mesothelioma. All had epithelioid pleural mesothelioma and a malignant pleural effusion. The findings may not apply to patients with biphasic or sarcomatoid tumors, peritoneal mesothelioma, or pleural mesothelioma without fluid buildup.
The study also had no control group. Researchers cannot directly compare the findings with outcomes from chemotherapy, immunotherapy, or supportive care.
Only nine patients with mesothelioma could be evaluated for disease control at 12 weeks. Most patients classified as having disease control had stable disease rather than tumor shrinkage.
The study was supported by RS Oncology, the company developing RSO-021. Several researchers disclosed financial or professional relationships with the company. Although the findings underwent peer review, independent research and larger controlled trials will be important.
According to RS Oncology, the phase 2 portion of the MITOPE study is complete, and the company expects to present results at an international oncology conference later in 2026. Those results have not yet been published or independently evaluated.
The phase 2 findings should provide additional information about:
Researchers are also developing newer PRX3 inhibitors that may be suitable for oral or intravenous administration. These drugs could potentially be studied in patients who do not have a pleural catheter or in cancers outside the chest. Until additional results are available, RSO-021 remains an experimental treatment rather than an approved option for mesothelioma.
Patients whose mesothelioma has progressed after standard treatment may want to ask a specialist about clinical trials. Eligibility can depend on the location of the cancer, cell type, previous treatments, overall health, and whether the patient has a malignant pleural effusion.
Questions to ask include:
Mesothelioma Hub can help patients and families connect with experienced mesothelioma doctors and cancer centers. A specialist can review an individual’s diagnosis and discuss standard treatments, symptom management, and available clinical trials. For families facing difficult decisions after mesothelioma has progressed, our free guide provides additional information about treatment, support resources, and potential financial assistance. Patients and loved ones can also request a free case evaluation to learn whether they may be eligible for compensation to help cover medical expenses and other costs associated with the disease.
Madeline works for the patient advocate team and writes about asbestos exposure and mesothelioma. She is passionate about helping families in the mesothelioma community.
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National Library of Medicine. (n.d.). Study of RSO-021 in patients with malignant pleural effusion due to advanced/metastatic solid tumors including mesothelioma (Clinical trial registration No. NCT05278975). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05278975
RS Oncology. (2026, July 14). RS Oncology’s PRX3 inhibitor (RSO-021) shows promise in fight against deadly mesothelioma, rooted in discovery science from the University of Vermont. https://www.rsoncology.com/companynews/preclinical-characterization-and-phase-1-clinical-testing-of-targeting-mitochondrial-peroxiredoxin-3-in-cancer