PI3Kδ Inhibitor Linperlisib Clinical Activity Among Patients With R/R Follicular Lymphoma

Results from a Single-Arm Phase 2 Trial

Linperlisib, an oral PI3Kδ inhibitor, displayed compelling clinical activity and manageable tolerability among patients with relapsed/refractory (R/R) follicular lymphoma (FL) who had received 2 or more prior systemic therapies, according to a phase 2 trial recently published in the American Association for Cancer Research Journal. 

Dr Tingyu Wang, MD, Peking Union Medical College, Tianjin, China, and coauthors aimed to assess the efficacy and safety of linperlisib for patients with R/R FL by observing a primary endpoint of objective response rate (ORR) and secondary endpoints including duration of response (DOR), overall survival (OS), disease control rate, as well as tolerability and safety. They stated, “a need remains for improved treatments that ideally minimize the risk for cumulative toxicities” of prior FL treatments as the impetus for this study.

84 patients with R/R FL with a median age of 51 years who had experienced disease progression after receiving 2 or more prior systemic therapy were enrolled in this study. Patients were given linperlisib orally at 80 mg daily in a 28-day cycle until either disease progression or toxicity occurred. For safety, antitumor response assessments were conducted every 2 cycles of administration. 

Results indicated that linperlisib was effective, as the patients reached an ORR of 79.8% (n=67), with 15.5% of patients (n=15) reaching a complete response and 64.3% of patients (n=54) reaching partial response. The median DOR was 12.3 months, and the median PFS was 13.4 months. At a 12-month follow-up, the OS rate was 91.4%. 

The most common grade ≥3 treatment-related adverse events were infectious pneumonia (19%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). 17.9% of patients (n=15) discontinued treatment due to adverse events, mainly associated with infectious pneumonia (10.7%). 

As both primary and secondary endpoints were met, Dr Wang et al concluded, “linperlisib demonstrated compelling clinical efficacy and exhibited a manageable safety profile, making it a valuable treatment modality for patients with relapsed and/or  refractory FL after at least [2] prior systemic treatments.” 

Source: 

Wang T, Sun Y, Qui L, et al. The oral PI3Kδ inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: a phase II, single-arm, open-label clinical trial. American Association for Cancer Research Journals. 2023:1557-3265. doi:https://doi.org/10.1158/1078-0432.CCR-22-2939