Tolerability and Clinical Benefit Assessment of Continuous Roginolisib Administration in Patients with Cancer including Metastatic Uveal Melanoma

Phosphatidylinositol 3-kinase delta (PI3Kδ) promotes tumour cell growth directly or indirectly by activating immune-suppressive cells. Roginolisib is a selective, non-ATP competitive inhibitor, which locks PI3Kδ into an inactive state. In a First-in-Human dose study, continuous daily dosing of roginolisib was investigated in patients with solid and haematologic malignancies. In Part A, 24 patients received escalating doses of roginolisib. In Part B, 20 mostly pre-treated metastatic uveal melanoma (mUM) patients received a dose associated with continuous PI3Kδ inhibition of > 90%. No Dose Limiting Toxicity or drug related toxicities requiring dose modifications were observed (≥ Grade 3 toxicities: 3/44; 6.8%). In mUM, median Overall Survival (mOS) was 20.8 months. mOS in mUM patients with Stable Disease was 28.5 months, and in patients with Progressive Disease was 12.3 months. Roginolisib treatment was associated with reducing T regulatory cell abundance, increasing activated CD8 ⁺ T cells and soluble plasma IL-15.