Copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms, has recently been shown to achieve a 59% objective tumor response rate (ORR) in a phase II study in patients with relapsed or refractory (r/r) indolent B-cell lymphoma. We report here the results of subgroup analyses conducted based on demographic and baseline disease characteristics.
Patients with indolent B-cell non-Hodgkin lymphoma (4 subtypes: follicular [FL], marginal zone [MZL], small lymphocytic [SLL] and lymphoplasmacytoid/Waldenström macroglobulinemia [LPL-WM]) and r/r to ≥ 2 prior lines of treatment were eligible. Previous treatment had to include rituximab and an alkylating agent. Copanlisib (60 mg, I.V.) was administered intermittently on days 1, 8 and 15 of a 28-day cycle. The primary efficacy endpoint was ORR as assessed per independent radiologic review (Cheson et al. 2007).
The full analysis set comprised 142 patients, of which 141 patients had indolent lymphoma (FL/MZL/SLL/LPL-WM: 104/23/8/6). ORR per histological subgroup was 58.7%/69.6%/75.0%/16.7%, respectively. ORR based on demographics were generally consistent across categories. Likewise, there were no major differences in ORR between any of the baseline disease characteristics and prior therapy subgroups with regards to ECOG PS (0 [58.8%] vs. ≥ 1 [59.7%]), longest diameter of baseline lesion (< 7cm [59.8%] vs. ≥ 7cm [59.1%]), received prior bendamustine (yes [62.7%] vs. no [56.6%]), number of prior therapies (< 4 [59.8%] vs. ≥ 4 [57.5%]), or refractoriness to last regimen (yes [60.5%] vs. no [57.1%]). Median duration of response (DOR) by tumor histology for the subgroups with ≥ 10 responders was 370 days (range 33-687) for FL patients and had not yet been reached for MZL patients (2 of 16 responders having progressed).
Objective response rates were consistently high in patients with r/r indolent B-cell lymphoma treated with copanlisib with the exception of LPL-WM patients. There were no major differences in the ORR between any of the baseline disease characteristics and prior therapy subgroups, confirming the robustness of the primary efficacy endpoint.
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Legal entity responsible for the study
T. Ishida: Employment: Bayer SA. L. Huang, J. Garcia-Vargas, B.H. Childs: Employment: Bayer HealthCare Pharmaceuticals Inc. M. Dreyling: Advisory boards: Bayer, Gilead Honoraria: Bayer, Gilead. All other authors have declared no conflicts of interest.