iOnctura has announced the dosing of the first patient in its randomized Phase II OCULE-01 study investigating roginolisib for the treatment of metastatic uveal melanoma (UM), a rare cancer of the eye with limited therapeutic options.
Roginolisib represents a new approach to targeting PI3Kδ through allosteric modulation, which promises to deliver clinical efficacy without the tolerability issues that have plagued previous generations of PI3Kδ inhibitors. The drug is administered orally and has shown promising results in earlier clinical testing.
Promising Phase I Results Drive Further Investigation
In the Phase I DIONE-01 study, roginolisib demonstrated an impressive safety profile and doubled overall survival in metastatic uveal melanoma patients compared to historical controls. The median overall survival reached 16 months in patients who had progressed on prior systemic therapy.
"Roginolisib has so far shown impressive tolerability and an interesting median overall survival of 16 months in patients with uveal melanoma who had progressed on prior systemic therapy," said Paul Nathan, Principal Investigator of the Phase II OCULE-01 study. "With roginolisib's attractive safety profile and the encouraging survival data observed in the first-in-human dose study, we look forward to continuing to investigate the potential of roginolisib in patients with limited therapeutic options."
OCULE-01 Trial Design and Objectives
The Phase II OCULE-01 study (NCT06717126) is designed as an open-label, randomized, parallel-arm trial that will evaluate roginolisib as a monotherapy. The primary objective is to assess overall survival in patients with metastatic uveal melanoma.
The trial will be conducted across multiple sites in Europe and the United States, with plans to enroll approximately 85 patients who have progressed following at least one prior therapy.
Secondary objectives of the study include assessment of:
- Progression-free survival
- Objective response rate
- Duration of response
- Time to response
- Disease control rate
- Clinical benefit rate
- Safety and tolerability
- Pharmacokinetics
- Healthcare utilization
- Quality of life
Regulatory Recognition Through Orphan Drug Designations
The potential of roginolisib in treating this rare cancer has been recognized by regulatory authorities on both sides of the Atlantic. In late 2024, the European Medicines Agency (EMA) granted Orphan Drug Designation (ODD) for roginolisib in the treatment of uveal melanoma. This designation provides significant benefits, including 10 years of market exclusivity in the European Union, protocol assistance, and fee reductions.
This European designation complements the ODD previously granted by the U.S. Food and Drug Administration (FDA) in early 2023, further validating the drug's potential in addressing this unmet medical need.
Market Potential and Future Directions
Uveal melanoma represents a significant market opportunity despite being a rare disease. According to Emergen Research, the eye melanoma market is projected to reach USD 9.56 billion by 2032, driven by the limited treatment options currently available.
Catherine Pickering, CEO and Co-Founder of iOnctura, highlighted the significance of this milestone: "We have achieved our first significant milestone for 2025 by starting one of several planned randomized Phase II studies for roginolisib. We are excited by the potential of roginolisib across a number of indications including uveal melanoma, non-small cell lung cancer and myelofibrosis, and we look forward to early data readouts by the end of the year."
The Science Behind Roginolisib
Roginolisib's mechanism of action as an allosteric modulator of PI3Kδ represents a novel approach to targeting this pathway. The PI3K signaling pathway is one of the most commonly dysregulated pathways across multiple cancer types, making it an attractive therapeutic target.
Traditional PI3Kδ inhibitors have been limited by tolerability issues, but roginolisib's unique chemical structure and binding mode may overcome these challenges. Allosteric modulation provides a more precise inhibition of PI3Kδ, potentially offering improved clinical outcomes without the side effects associated with earlier generations of inhibitors.
Beyond uveal melanoma, iOnctura is exploring roginolisib's potential in other indications, including non-small cell lung cancer and myelofibrosis, with additional Phase II studies being initiated.
About iOnctura
iOnctura is a clinical-stage precision oncology company focused on developing treatments for neglected and hard-to-treat cancers. The company's pipeline consists of first-in-class small molecules designed to extend lives and improve health outcomes for patients.
Headquartered in Amsterdam, The Netherlands, with a Swiss subsidiary in Geneva, iOnctura is backed by specialist institutional investors including Syncona, M Ventures, Inkef Capital, EIC Fund, VI Partners, Schroders Capital, and XGEN Venture.
As the OCULE-01 trial progresses, the oncology community will be watching closely to see if roginolisib can deliver on its early promise and potentially become a new standard of care for patients with metastatic uveal melanoma.
