A Phase Ib Study of Linperlisib in the Treatment of Patients with Relapsed and/or Refractory Peripheral T-cell Lymphoma

Abstract Purpose: Relapsed and/or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive and heterogeneous hematologic malignancy with high unmet need. Previously, PI3K inhibitors were shown to be efficacious in B- and T-cell lymphomas, but as a drug class, these agents have frequently been observed to have tolerability limitations. Next-generation agents that improve the tolerability while maintaining efficacy are desirable. Patients and Methods: A phase Ib clinical study was conducted with the oral PI3K-delta isoform-selective small-molecule inhibitor, linperlisib, in patients with r/r PTCL, and the clinical benefit was explored by the evaluation of safety and efficacy. Results: In this clinical study, 43 patients with r/r PTCL in China were treated with continuous dosing of 80-mg linperlisib once a day. Treatment-related adverse events (AE) were manageable. The most frequently reported grade 3 AE were neutropenia (21%), pneumonia (11.6%), and hypertriglyceridemia (7%). All other AE were either absent or reported in <5% of the patients. Linperlisib treatment for these patients with r/r PTCL, consisting of the major PTCL subtypes, was observed to have a 60.5% overall response rate with 35% complete responses and led to a median duration of response of 11.1 months, median progression-free survival of 11.8 months, and a median overall survival of >38 months (not reached). Conclusions: With the very promising clinical activity against r/r PTCL, the results of this study support the further investigation of linperlisib for the treatment of r/r PTCL.