The oral PI3Kdelta inhibitor linperlisib for the treatment of relapsed and/or refractory follicular lymphoma: A phase 2, single-arm, open-label clinical trial
Mené sur 84 patients atteints d'un lymphome folliculaire réfractaire et/ou récidivant, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du linperlisib, un inhibiteur de PI3Kdelta dispensé par voie orale, après l'échec d'au moins deux lignes thérapeutiques
Purpose: To investigate the efficacy and safety of the novel orally active phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor in relapsed and/or refractory follicular lymphoma (FL) patients who had received at least two prior systemic treatments. Patients and Methods: Histologically confirmed relapsed and/or refractory FL patients with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg qd, po in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression free survival (PFS), overall survival (OS), disease control rate and drug safety profile. Of 114 screened relapsed and/or refractory FL patients, 84 were enrolled in the full analysis set (FAS). Results: The ORR of 84 FAS patients was 79.8% (95%CI: 69.6-87.8, 67 patients), with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (range: 9.3-15.9). The median PFS was 13.4 months (95%CI: 11.1-16.7). The 12-month OS rate was 91.4% (95%CI: 82.7-95.8. and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events grade ≥3 were infectious pneumonia (19.0%), 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%). Conclusions: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory FL patients who had received at least two prior systemic therapies.