Dr Nathan on the Rationale for Evaluating Roginolisib in Advanced Ocular or Uveal Melanoma

“Uveal melanoma is an area of huge unmet need. Huge in terms of the amount of need, rather than the number of patients, because it’s a relatively rare disease. For these patients, we struggle to keep them well for a long time.”

Paul Nathan, MBBS, PhD, MRCP, a consultant medical oncologist at The Mount Vernon Cancer Centre, detailed the impetus for evaluating roginolisib for the treatment of patients with advanced or metastatic ocular or uveal melanoma.

The overactivation of thePI3Kδ pathway is caused by a rare inherited condition, which also leads patients to experience immunosuppression, Nathan began. He noted that the pathway appears activated in several tumors, which could be involved in making immune responses to the suppressed tumor. This leads to a balance change in the T regulatory (Treg) cells compared with cytotoxic T cells and therefore changes the immune microenvironment and suppresses immune responses, he explained.

Roginolisib is a novel small-molecule inhibitor of PI3Kδ, which is an isoform of the PI3K enzyme, Nathan continued. Preliminary data have demonstrated that it could change the immune microenvironment in cancers to become an activated environment, he asserted. When this occurs, reductions in Treg infiltrate and changes in myeloid suppressor cells were observed, he said.

Furthermore, uveal melanoma is considered a rare form of cancer, which reflects a significant unmet need, particularly with fewer modalities to provide long-term care, Nathan emphasized. However, early data with roginolisib have demonstrated reversals in Treg and CD8 ratios and preliminary signs of clinical benefit among patients on the study, he explained.

Of note, the phase 2 OCULE-01 (NCT06717126) is evaluating the efficacy of roginolisib at 80 mg once daily compared with investigator choice in patients with ocular or uveal melanoma who have previously been treated with at least 1 immunotherapy. Patients included on the study are at least 18 years of age, have advanced or metastatic uveal melanoma or ocular melanoma, have at least 1 suitable lesion for biopsy, at least 1 measurable lesion per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1.