The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial

Abstract

Purpose: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments.

Patients and methods: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally 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.

Results: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (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 (95% CI, 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 patients with FL who had received at least two prior systemic therapies.

Figure 1.

Flowchart of the study.

Figure 2.

Response outcomes and linperlisib treatment in relapsed and/or refractory FL. A, Waterfall plot of tumor change from baseline and best responses (CR, PR, SD, or PD); on the x-axis, each bar is an individual patient. B, A swimmer plot representing the duration of treatment, PFS for each patient on the y-axis and including best response (CR, PR, SD, or PD) to linperlisib; each bar is an individual patient. Timing of first response, death, and discontinuation are noted. A 12-month (1 year) indicator is represented with the blue dashed line. DOR (C), PFS (D), and OS (E) based on IRC assessment.

Figure 3.

Subgroup analysis of ORR, DOR, and PFS confirmed by IRC assessment for patients with FL demographic and baseline criteria. Forest plots for a variety of relapsed and/or refractory patients with FL characteristics are shown for the linperlisib phase II study. ORR (A), DOR (B), and PFS (C). Vertical line represents the median value for ORR, DOR, and PFS for all patients. P values and odds ratio (ORR only) are shown as calculated between the two subgroups for any parameter displayed. Note: In cases where patients had a censor endpoint, the confidence intervals were unable to be calculated, and only the median value is displayed for that subgroup evaluation.