iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, provides a clinical update on its lead asset, roginolisib.
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Results from the completed Phase I DIONE-01 study were presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) annual congress on 12th December.
Allosteric modulator of PI3Kδ, roginolisib, has a chemical structure and binding mechanism which makes it highly specific for PI3Kδ, giving it an advantageous pharmacology profile and an unprecedented safety profile compared to previous generations of PI3Kδ inhibitors.
Roginolisib is being investigated in solid and hematological malignancies including uveal melanoma (UM), a rare cancer of the eye. Eye melanoma is a rapidly growing market which is projected to be worth $9.56B by 2032.
The two-part Phase I study DIONE-01, firstly evaluated continuous daily dosing of roginolisib [at 10, 20, 40 and 80 mg] in 24 patients with pretreated solid tumours and follicular lymphoma (FL), and secondly evaluated a dose confirmation cohort in 20 UM patients.
Results from DIONE-01 show:
- Study met its primary objective to determine the safety of the anticipated optimal biologically effective dose (BED): Roginolisib was well tolerated at the recommended Phase II dose (RP2D) of 80mg, with <7% Grade 3/4 treatment-emergent adverse events (TEAEs) considered to be related to roginolisib. TEAEs did not result in immune-related toxicity, or dose-limiting toxicity, in either solid tumor or hematological patients. In contrast to prior PI3Kδ inhibitors, roginolisib dosing did not require dose modifications.
- Roginolisib is well tolerated over long periods of treatment, up to 4.5 years.
- Median overall survival (OS) was 16 months for the 29 patients with UM treated with roginolisib, who had previously received a median of two prior therapies. This exceeds the median OS of 7 months observed in historical controls in patients receiving immunotherapies as second line treatment[2].
- Median progression free survival (PFS) was 5 months for patients treated with roginolisib versus less than 3 months for historical controls.
- Clinical findings validate the mechanism of action of roginolisib: roginolisib reduces immune-suppressive immune cells and chemokines, UM-related tumour clones (ctDNA) and PI3K-related signalling indicating a rebalancing of the immune system.
Catherine Pickering, chief executive officer of iOnctura, said: “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. We are delighted to announce these data support progression of roginolisib into a randomised Phase II study.”