CAMBRIDGE, MA — RS Oncology today announced positive clinical results from its Phase I/II dose expansion study (MITOPE, NCT05278975) evaluating RSO-021 (a novel PRX3 inhibitor). The phase 2 portion of the study enrolled patients with pleural mesothelioma (PM) and other solid tumors that presented with a pleural effusion. The data demonstrates that a weekly dose of RSO-021 provides durable disease control, improved progression-free survival (PFS) and overall survival (OS), with a manageable safety profile.
“These results are incredibly encouraging because they represent the clinical validation of a biological vulnerability we first identified in mesothelioma cells in the laboratory,” said Brian Cunniff, Ph.D., a member of the University of Vermont Cancer Center and associate professor at the Larner College of Medicine. “To see a discovery that began with fundamental questions about how these tumor cells survive now showing promising results in patients is deeply rewarding. Most importantly, these findings give us confidence in moving this novel therapeutic approach forward for patients who urgently need better treatment options.”
RSO-021 originated from research at the University of Vermont Cancer Center, where Cunniff and colleagues identified a mitochondrial vulnerability in mesothelioma cells and showed that RSO-021 could exploit it to kill tumor cells. The Cunniff Lab provided the scientific foundation in supporting the basic and translational research behind RS Oncology's clinical program.
"The successful completion of our Phase 2 clinical trial marks an important milestone in our mission to deliver meaningful and innovative therapies to patients and their families impacted by pleural mesothelioma,” said RS Oncology, CEO, Jarrett Duncan. “By developing a targeted and novel therapy designed to inhibit PRX3, we are seeing significant improvements in overall survival benefits with manageable side effects for patients facing this aggressive disease. Driven by this remarkable momentum in collaboration with UVM, we are working to advance this novel therapy further in our Phase 3 study, which we believe will validate the full potential of this program and improve the treatment options for patients in the UK and beyond."
“The safety, tolerability and overall survival data from the Phase 2 trial of RSO-021 are encouraging,” said Dr. Sean Dulloo, Consultant Medical Oncologist, MITOPE trial Principal Investigator. “The results represent a meaningful signal of clinical benefit and reinforce our commitment to advancing RSO-021 as a potential new treatment option for patients.”
Innovative Mechanism Targeting Mesothelioma
RSO-021 is a novel therapeutic that inactivates the mitochondrial enzyme PRX3. By doing so, it induces oxidative stress that directly suppresses mesothelioma tumor cell growth. Because approximately 80% of mesothelioma patients present with a pleural effusion at diagnosis, administering RSO-021 loco-regionally via an indwelling intrapleural catheter (IPC) offers a major opportunity to treat the cancer directly at the tumor site prior to systemic therapy.
Key Clinical Trial Findings
The study evaluated 41 patients who received weekly intrapleural doses of either 45 mg (n=18) or 90 mg (n=23) of RSO-021. Of the 41 total patients, 32 were within the Window of Opportunity (WoO) setting (frontline treatment before standard of care).
Enhanced Progression-Free Survival (PFS) at 90 mg: Patients across the entire Phase 1/2 study on the 90 mg dose experienced a median PFS of 4.1 months, compared to 3.1 months for those on the 45 mg dose.
Overall Survival (OS): Specific to the WoO setting, the median overall survival was not yet reached at 90mg (>23 months at study closure, August 2026) vs 12.8 months at 45 mg.
Tumor Response: 70% of participants in the WoO setting reached a best overall response of either partial response (PR) or stable disease (SD). Most participants with SD also showed a reduction in the sum of diameters of their lesions. There was 52% durable disease control at 90 mg and 31% at 45 mg, with some participants remaining on treatment for over 10 cycles.
Treatment Exposure: High variability of RSO-021 was observed in pleural effusion drainage; this is likely linked to differing amounts of pleural effusion fluid drainage in each patient. Concentrations of pleural fluid ranged from approximately 5,000 to 195,000 ng/mL. Much lower concentrations, ranging from 212 to 1,300 ng/mL were observed in some participants on specific occasions. The exposure at 90 mg was substantially higher than 45 mg, with similar relative dose intensity. In plasma, levels of RSO-021 remained extremely low.
Manageable Safety Profile
The overall safety profile was consistent with a population of patients with MPE, reporting infectious and respiratory events, many events regarding the IP catheter used for pleural drainage and RSO-021 infusion. Most common TEAEs were less than or equal to grade 3 and being catheter site infection, dyspnea, and pneumonia. The TREs that occurred in 56% of patients were mostly grade 1 or 2, 3 grade 3 (chest pain, nausea), and 1 grade 4 (neutropenia). SAEs in 61% and 44% of patients receiving 90 mg and 45 mg, respectively (pneumonia in 13 vs 0%). There were no treatment-related deaths.
Conclusion & Next Steps
Preliminary efficacy signals were observed, with more than half of evaluable patients with pleural mesothelioma achieving a BOR of PR or SD and reductions in target lesion diameters in most responders. The low incidence of treatment-related AEs, high-grade treatment-emergent AEs and lack of treatment-related deaths, along with the efficacy and exposure data, support selection of the 90 mg dose for further clinical development.
The OS observed in the MITOPE phase 1-2 study is favorable in early-stage (1-2) mesothelioma compared to late-stage (3+) patients. Additionally, there is currently no established SOC treatment for early-stage pleural mesothelioma and systemic therapies are restricted to unresectable disease, which largely presents in the later stages.
Continued development of RSO-021 in early-stage mesothelioma patients has the potential to transform the patient treatment landscape and offer patients who are diagnosed with early-stage pleural mesothelioma (>50% of patients in the UK and elsewhere), a treatment option where there currently is none.
About RS Oncology
RS Oncology is a clinical-stage biotechnology company committed to developing innovative therapies for patients with aggressive, hard-to-treat cancers. By targeting mitochondrial pathways and leveraging localized delivery mechanisms, RS Oncology aims to deliver impactful treatments that improve patient outcomes.
Media Contact
Jarrett Duncan
CEO
RS Oncology
j.duncan@rsoncology.com
rsoncology.com