Phase Ib study of the oral PI3Kδ inhibitor linperlisib in patients with advanced solid tumors.

Background: Patients with advanced solid tumors have a suboptimal prognosis. This study investigated the safety and feasibility of linperlisib, a selective phosphatidylinositol 3-kinase delta isoform (PI3Kδ) inhibitor, for treating patients with advanced solid tumors.

Methods: In this phase Ib, single-arm, open-label, multi-center clinical trial, patients with histologically confirmed advanced solid tumors from eight centers in China were enrolled to receive oral linperlisib (80 mg/day). The primary endpoint was safety.

Results: Between August 2019 and June 2022, 94 patients were enrolled in the trial and received the study treatment. The most common (≥ 20%) treatment emergent adverse events (TEAEs) of all grades irrespective of causality were increased aspartate aminotransferase (AST) (26.6%), proteinuria (26.6%), decreased appetite (25.5%), increased alanine aminotransferase (ALT) (22.3%), weight loss (21.3%), and anemia (21.3%). The most common grade ≥ 3 TEAEs were diarrhea (4.3%), increased AST (3.2%), increased ALT (3.2%), neutropenia (3.2%), anemia (3.2%), increased blood alkaline phosphatase (3.2%). The objective response rate (ORR) was 1.1% (95% confidence interval [CI] 0.0-5.8), and the disease control rate (DCR) was 37.2% (95% CI 27.5-47.8). As of the data cutoff, the median follow-up time was 4.2 months (95% CI 2.8-6.9). The median progression-free survival (PFS) was 1.85 months (95% CI 1.79-1.88). The median overall survival (OS) was not reached.

Conclusion: Linperlisib showed an acceptable safety profile and preliminary clinical benefit in patients with a range of advanced solid tumors. Further studies of linperlisib safety and efficacy are warranted.