RSO-021 controlled malignant pleural effusion in 67% of patients at 12 weeks
A Phase 1 trial of the PRX3 inhibitor RSO-021, delivered directly into the pleural space, met its safety and dose-finding goals in mesothelioma-related effusion.
Executive Summary
- A Phase 1 trial tested whether locally delivered inhibition of a mitochondrial antioxidant enzyme could be given safely to patients with malignant pleural effusion from mesothelioma and other tumors, and at what dose.
- The regimen was tolerated at its tested dose, met its safety and dose-finding goals, and produced disease control along with tumor reductions in a majority of patients followed to 12 weeks.
- Mesothelioma-associated pleural effusion has few treatment options once standard therapy fails, and a local, redox-targeting approach delivered directly into the pleural space offers a mechanism distinct from systemic chemotherapy or immunotherapy.
- A genomic marker of resistance to the drug was identified in this cohort, opening a rationale for combination approaches that the trial's secondary measures did not yet test.
The finding
Weekly intrapleural dosing of RSO-021 at 90 mg was tolerated in patients with malignant pleural effusion from relapsed mesothelioma and other advanced tumors, researchers reported. The trial's three primary endpoints, safety, dose-limiting toxicity, and frequency and severity of adverse events, were met, and disease control was observed in 67% of patients at the 12-week assessment, with tumor reductions reported in the same cohort. The drug is a formulated version of thiostrepton, a sulfur-rich cyclic peptide that covalently inhibits PRX3, an enzyme cancer cells rely on to manage oxidative stress. Preclinical+1Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.Jul 14, 2026Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including MesotheliomaNCT05278975
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
How it was done
The study is a Phase 1/2, open-label, non-randomized trial run across sites in the United Kingdom, enrolling adults with ECOG performance status 0-1 and a pleural disease burden that made intrapleural drug delivery feasible. The Phase 1 dose-escalation stage assessed dose-limiting toxicity over the first 21 days and adverse events through 90 days after the last dose, using RSO-021 delivered through an indwelling pleural catheter on a weekly schedule. Secondary measures, including objective response rate, disease control rate, progression-free survival, and pharmacokinetics, were tracked through 90 days post-dosing. The trial recruits across five arms spanning dose escalation and four expansion cohorts covering non-mesothelioma and mesothelioma populations, including a first-line window-of-opportunity cohort ahead of systemic therapy. NCT05278975Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including MesotheliomaNCT05278975
The mechanism, and its limit
The preclinical work behind the trial showed that genetically deleting PRX3 impaired mitochondrial energy production and slowed mesothelioma growth in laboratory models, and that thiostrepton reproduced this effect by inducing cell death in patient-derived mesothelioma tissue explants. Genomic screening in the same program identified Solute Carrier Family 7 member 11 (SLC7A11) as a mediator of resistance to thiostrepton, a finding the authors say suggests that combining RSO-021 with a therapy targeting that transporter could deepen the drug's pro-oxidant effect. That combination has not been tested in this trial and remains a stated direction for future work rather than a demonstrated result. PreclinicalPreclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.Jul 14, 2026
Where this sits
Malignant pleural effusion carries few approved local treatments; talc pleurodesis and bleomycin are cleared for reducing effusion recurrence, but neither targets the underlying tumor biology the way an antioxidant-pathway inhibitor does. Registered interventional trials in this indication remain sparse, and RSO-021 is the only Peptide-modality agent identified in Malignant Pleural Effusion trials to date. That leaves this readout without a direct comparator on the same delivery route or mechanism; its closest points of reference are the broader field of intrapleural and systemic therapies tested in mesothelioma and lung malignancies rather than any agent sharing its target. NCT05278975Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including MesotheliomaNCT05278975
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.