iOnctura has announced promising results from its Phase I DIONE-01 study, revealing that roginolisib, an allosteric modulator of PI3Kδ, significantly improved overall survival in patients with uveal melanoma (UM). The study's findings, presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) annual congress, highlight roginolisib's potential as a novel treatment for this rare eye cancer.
The DIONE-01 trial, a two-part Phase I study, initially evaluated continuous daily dosing of roginolisib (10, 20, 40, and 80 mg) in 24 patients with pretreated solid tumors and follicular lymphoma. Subsequently, a dose confirmation cohort of 20 UM patients was assessed. The results indicated that roginolisib was well-tolerated at the recommended Phase II dose (RP2D) of 80mg, with less than 7% of patients experiencing Grade 3/4 treatment-emergent adverse events (TEAEs) considered related to the drug. Notably, roginolisib dosing did not require modifications, unlike previous PI3Kδ inhibitors.
Survival Benefits and Tolerability
The study's most striking finding was the median overall survival (OS) of 16 months in UM patients treated with roginolisib, who had previously received a median of two prior therapies. This represents a doubling of the median OS compared to the 7 months observed in historical controls receiving immunotherapies as second-line treatment. Additionally, the median progression-free survival (PFS) was 5 months for patients on roginolisib, compared to less than 3 months in historical controls.
Catherine Pickering, CEO of iOnctura, emphasized the significance of these results, stating, "The Phase I DIONE-01 data highlight the benefits of roginolisib for patients with uveal melanoma and advanced cancers. Roginolisib's unique allosteric binding mechanism has translated into a differentiated beneficial clinical profile, including a doubling of overall survival compared to historical controls in uveal melanoma."
Mechanism of Action and Ongoing Phase II Trial
Clinical findings from the DIONE-01 study also validated roginolisib's mechanism of action, demonstrating its ability to reduce immune-suppressive immune cells and chemokines, UM-related tumor clones (ctDNA), and PI3K-related signaling, indicating a rebalancing of the immune system.
Building on these promising results, iOnctura is advancing roginolisib into a randomized Phase II OCULE-01 study (NCT06717126). This trial will investigate roginolisib versus investigator's choice in the second-line+ treatment of uveal melanoma. Trial site activation is currently underway.
Professor Michele Maio, Principal Investigator of the roginolisib studies, commented, "Being able to continue to investigate roginolisib in a randomized Phase II study is a positive step to understand more about this already well tolerated molecule. Roginolisib has given prolonged disease stabilization to patients with uveal melanoma who have exhausted all other therapeutic options. So far, these patients have maintained a good quality of life without major limitations."
