Mesothelioma Drug RSO-021 Controlled Disease in 6 of 9 People
RSO-021 controlled disease in 6 of 9 evaluable people at 12 weeks in a phase 1 trial. The full results, and what they don't yet show.
Researchers at the University of Vermont and RS Oncology have published the first human results for a drug called RSO-021. It doesn’t attack the tumor directly. It overwhelms the tumor’s own defenses against stress until the cancer cell can’t cope. The results appeared in Nature Communications on July 14, 2026.
In the phase 1 trial, 6 of 9 evaluable people had their disease under control at 12 weeks on the 90 milligram dose. The study also found which tumors responded in laboratory testing, and which ones resisted.
If you or someone in your family is living with mesothelioma, here’s what the trial found, and what it doesn’t yet tell us.
How the Drug Works
Cancer cells burn through energy quickly, and that process throws off unstable molecules called reactive oxygen species. Left alone, those molecules damage the cell. Tumors survive by producing antioxidant enzymes that mop them up.
One of those enzymes is peroxiredoxin 3, or PRX3. It works inside mitochondria, the compartments that generate a cell’s energy, where it clears hydrogen peroxide produced during metabolism.
Most cancer research has tried to reduce this kind of cellular stress. This work does the opposite. It blocks PRX3 so hydrogen peroxide builds up inside the tumor’s mitochondria until the cell can’t cope.
Mesothelioma cells already run at high levels of oxidative stress. So the research team expected them to hit that limit before healthy cells do.
RSO-021 is a clinical formulation of thiostrepton, an antibiotic identified decades ago. It binds to PRX3 and shuts it down.
What the Trial Tested
The trial (NCT05278975) enrolled people whose pleural mesothelioma had come back after standard treatment. All of them also had fluid building up around the lung, a condition called malignant pleural effusion.
The team didn’t give the drug by mouth or by infusion. They delivered it straight into the space around the lung through an indwelling pleural catheter, once a week. That concentrates the drug where the tumor is and limits how much reaches the rest of the body.
Fifteen people received the drug in the phase 1 portion. Twelve had pleural mesothelioma. The other three had colorectal cancer or non-small cell lung cancer. Every person with mesothelioma had epithelioid disease and had already been through standard care without lasting benefit.
What the Results Showed
The trial’s main goals were safety and finding the right dose. It met both.
At 90 milligrams, none of the seven people treated had a dose-limiting toxicity. At 120 milligrams, two of six did. One had a grade 3 inflammatory response, the other grade 3 shortness of breath. One of the two people treated at 180 milligrams had grade 3 breathlessness.
That pattern set 90 milligrams as the dose carried forward. Almost every side effect recorded across the trial was mild or moderate, and fatigue was the most common at 33.3% across all dose levels.
On the effectiveness measures, which phase 1 trials explore rather than prove:
- One of the 10 people evaluable for response had a partial response, meaning the tumor measurably shrank. That person received the 90 milligram dose, and the response lasted until week 30.
- By 12 weeks, 6 of 9 evaluable people had disease control, counting that one partial response plus five people whose disease held steady.
- Median progression-free survival was 18 weeks among the 9 people in the assessable efficacy group.
- Overall survival was not reached at 80 weeks among the 12 people with mesothelioma. Seven of them were still alive when the data was collected.
That last figure is the one most likely to be misread, so it’s worth spelling out.
When researchers say median overall survival was “not reached,” they mean more than half the group was still living when the data was counted. A median can’t be calculated yet. It’s a signal worth following, but it isn’t a survival figure, and you can’t compare a single-arm trial of 12 people against survival numbers from other treatments.
The Finding About Who Responded
Alongside the trial, the team tested tumor tissue from 22 people, collected during routine surgery, and treated it in the laboratory to see which samples died and which held on.
Tumors carrying damage to two genes were significantly more likely to respond. Alterations in BAP1 appeared more often in responding tissue (p = 0.0124), as did alterations in SETD2 (p = 0.03). Both genes sit in the same stretch of chromosome 3 that is frequently altered in mesothelioma, and BAP1 in particular is already one of the most studied genes in the disease.
This is a laboratory result from tumor tissue, not a result from people treated in the trial. It hasn’t been used to choose who gets treatment. But it points toward a future where a tumor’s genetic profile could show whether this class of drug is worth trying. That connects to the genetic testing already used in mesothelioma care, which many families have encountered through BAP1 testing.
The researchers also found the opposite signal. Tumors producing higher levels of a protein called SLC7A11 resisted the drug, because that protein helps a cell build additional antioxidant defenses that compensate when PRX3 is blocked. In laboratory testing, pairing the PRX3 inhibitor with a drug that blocks SLC7A11 killed noticeably more cancer cells.
What These Results Don’t Show
If you’re reading about this drug while weighing your own options, five limits matter.
The trial has closed. ClinicalTrials.gov records the study as completed, with the final data collected on May 7, 2026. You can’t enroll in it.
It ran only in the United Kingdom. All ten listed sites were NHS hospitals, including the Royal Marsden, the Christie, Barts Health, and centers in Bristol, Leeds, Glasgow, Leicester, Oxford, and Northumbria. No site in the United States took part.
The numbers are small. Nine people contributed to the 12-week disease-control figure and 12 people to the survival data. Results from groups this size shift as more people are studied.
Phase 2 results aren’t out. The trial included four phase 2 expansion groups. One tested the drug before immunotherapy rather than after standard care failed. Those results haven’t been published, so nothing can be said about them yet.
This isn’t an approved treatment. RSO-021 is investigational. Regulators haven’t approved it for mesothelioma or any other condition.
A separate paper in Science Advances in October 2025, from many of the same researchers, described a next generation of PRX3 inhibitors built around the same mechanism. That work is at the laboratory stage.
Because this study has closed, your practical next step is to ask your oncology team what’s open now. ClinicalTrials.gov lists active mesothelioma studies and you can filter them by location. Your oncologist can tell you which ones fit your diagnosis and treatment history.
Why This Approach Is Different
Most mesothelioma treatment falls into surgery, chemotherapy, and immune checkpoint inhibitors, and several newer experimental drugs target the Hippo pathway that governs cell growth. RSO-021 goes somewhere else entirely. It targets how the tumor manages its internal chemistry.
The team reported that the drug appears to do two things at once. It kills tumor cells directly, and it may also change how the immune system engages the tumor. The researchers are now studying whether the same approach works in other cancers, including gastric cancer and peritoneal mesothelioma, and are developing versions of the drug that might be taken by mouth.
References
Nature Communications. Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.
https://pmc.ncbi.nlm.nih.gov/articles/PMC13369167/
ClinicalTrials.gov. A Translational Phase 1/2 Study of RSO-021 in Patients With Malignant Pleural Effusion (NCT05278975).
https://clinicaltrials.gov/study/NCT05278975
Science Advances. Mechanism-based peroxiredoxin 3 inhibitors exploit a covalent warhead for cancer therapy.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12577686/
Reader Q&A
Frequently Asked Questions
What is RSO-021?
RSO-021 is an investigational drug developed by RS Oncology with researchers at the University of Vermont. It’s a clinical formulation of thiostrepton, an antibiotic, and it blocks an enzyme called peroxiredoxin 3 that mesothelioma cells rely on to survive their own oxidative stress. It’s given directly into the space around the lung.
How well did RSO-021 work in its first trial?
At 12 weeks, 6 of 9 evaluable people had disease control at the 90 milligram dose, which counted one partial response and five people whose disease stayed stable. Median progression-free survival was 18 weeks among 9 people, and median overall survival had not been reached at 80 weeks among the 12 people with mesothelioma. These are early findings from a small phase 1 trial designed mainly to test safety.
Can I join the RSO-021 trial?
No. ClinicalTrials.gov records trial NCT05278975 as completed, with data collection finishing on May 7, 2026. The trial also ran only at hospitals in the United Kingdom. Anyone looking for a current study can search ClinicalTrials.gov and talk with their oncologist about what’s open and appropriate.
What does BAP1 have to do with this drug?
In laboratory testing on tumor tissue from 22 people, samples with alterations in the BAP1 gene were significantly more likely to respond to the drug (p = 0.0124). The same held for samples with alterations in SETD2 (p = 0.03). This came from tissue tested outside the body, not from people treated in the trial. So it isn’t yet used to decide who gets the drug. It’s a lead for future research.
Why did some tumors resist RSO-021?
Tumors with higher levels of a protein called SLC7A11 were more resistant. That protein helps cells produce extra antioxidants, which offsets the effect of blocking PRX3. When researchers combined the PRX3 inhibitor with a drug blocking SLC7A11 in the laboratory, more cancer cells died, which suggests a possible combination approach for future study.
Is RSO-021 approved for mesothelioma?
No. RSO-021 is investigational, and the FDA hasn’t approved it for mesothelioma or any other condition. Neither has any other regulator. It’s completed phase 1 testing, and phase 2 results haven’t been published.