The conformation-selective PI3Kδ inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial.

Roginolisib demonstrates safety and achieves over 90% continuous PI3Kδ inhibition in patients with advanced cancers, including metastatic uveal melanoma, with median OS of 20.8 months.

• Why it matters: Effective PI3Kδ inhibition could improve outcomes in cancers driven by tumor growth and immune suppression, addressing the need for targeted therapies with manageable safety profiles.
• What they did: The first-in-human trial involved 44 patients receiving escalating doses of roginolisib, including 20 with metastatic uveal melanoma, assessing safety, PK/PD, and clinical responses, with exploratory immunophenotyping, proteomics, and genomics.
• The result: Roginolisib was well tolerated without dose-limiting toxicities, and in metastatic uveal melanoma, patients with stable disease at Week 16 had a median OS of 28.5 months, indicating potential clinical benefit.