Background: The orally active phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor linperlisib which conveyed acceptable safety and notable efficacy for B-cell lymphoma medications in a previous phase 1 dose escalation study was investigated in this phase 2 study for the treatment of relapsed and/or refractory follicular lymphoma (FL) patients who had received at least two prior systemic treatments
Aims: To explore the satefy and efficacy of linperlisib in FL
Methods: Linperlisib was administered at 80 mg qd, po in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome was the objective response rate (ORR), while secondary outcomes included the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and the drug safety profile.
Results: For 84 FL patients in the full analysis set (FAS) the ORR was 79.8% (95% CI: 69.6-87.8, 67 patients), with 13 patients achieving a complete response and 54 a partial response. The median DOR was 12.3 months (range, 9.3-15.9) with 6-month and 12-month DORs of 80.0% (95% CI: 67.4-88.1) and 55.3% (95% CI: 40.6-67.8). The median PFS was 13.4 months (95% CI: 11.1-16.7), with 6-month and 12-month PFS rates of 78.7% (95% CI: 67.5-86.3) and 53.1% (95% CI: 40.3-64.3). The median OS was not reached, while 6-month and 12-month OS rates were 97.6% (95% CI: 90.6-99.4) and 91.4% (95% CI: 82.7-95.8), respectively. The most frequent any-grade treatment related AEs (TRAE) were neutropenia (47%), hypertriglyceridemia (25%), while the most frequent TRAEs ≥ grade 3 were neutropenia (15%), infectious pneumonia (19.4%) and interstitial lung disease (6.5%). AEs that were potentially immune-mediated, such as diarrhea, colitis, pneumonitis, and transaminitis, were observed at significantly lower incidences of occurrence.
Summary/Conclusion: Linperlisib demonstrated compelling clinical efficacy and a promising safety profile, which has the potential to surpass the approved PI3K inhibitors for the treatment of relapsed or refractory FL patients after two prior therapies.