Copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with potent PI3K-α and PI3K-δ activity, has been explored as monotherapy in four phase I or II studies in patients with relapsed or refractory (r/r) indolent B-cell lymphoma having progressed on two or more prior lines of therapy. Because of similar entry criteria for all four studies, we therefore conducted a combined safety and efficacy analysis.
Patients with indolent B-cell non-Hodgkin lymphoma and r/r to ≥ 2 prior lines of treatment were eligible. Previous treatment included rituximab and an alkylating agent. Copanlisib was administered intravenously intermittently on days 1, 8 and 15 of a 28-day cycle at either 0.8 mg/kg (studies NCT00962611, NCT02155582, and NCT01660451-A) or as a flat 60 mg dose (NCT01660451-B). The primary efficacy endpoint was objective response rate (ORR) using Cheson criteria based on central independent review and/or investigator assessment.
The full analysis set comprised 168 patients, with follicular (n = 126) and marginal zone (n = 26), being the most common lymphoma sub-types. The median age was 64 (range 25-82), with ECOG status 0/1 being 56%/40%. The most common grade (G) 3/4 treatment emergent adverse events (AEs) were transient hyperglycemia (32%/6%, respectively) and transient hypertension (27%/0, respectively). Other all-grade AEs (all-grade%/G3%/G4%) occurring in > 25% of patients included diarrhea (36/5/0), fatigue (29/3/0), and nausea (26/1/0). Serious AEs of interest included pneumonia (10/7/1), pneumonitis (6/3/0) and one case of colitis (G4). The ORR for the entire dataset was 60%, with 21 (12%) patients with complete responses (CR; 1 uCR), 79 (47%) with partial responses (PR), and 51 (30%) with stable disease (SD). Based on investigator assessments, the ORR was 54%, with 9 (5%) CR, 81 (48%) PR, and 54 (32%) SD.
Treatment of indolent B-cell lymphoma patients with copanlisib administered intermittently and intravenously resulted in a manageable and predictable safety profile, with a low incidence of severe GI-related toxicities. The ORR for indolent lymphoma patients treated with copanlisib was robust by both independent and investigator analysis.
Clinical trial identification
NCT00962611, NCT02155582, NCT01660451.
Legal entity responsible for the study
A. Santoro: Advisory board: Bayer, Roche, Novartis, BMS, MSD, Lilly, AstraZeneca, Servier. L. Huang, F. Hiemeyer, A. Benson, I. Genvresse, J.E. Garcia-Vargas, B.H. Childs: Employee: Bayer. M.H. Dreyling: Research funding: Bayer. All other authors have declared no conflicts of interest.