Copanlisib Treatment of Aggressive Lymphoma: Subset Analysis of Relapsed / Refractory Peripheral T-Cell Lymphoma Patients from a Phase II Trial

Introduction: Peripheral T-cell lymphomas (PTCL) generally have poor clinical outcomes. Preclinical data indicate that the phosphatidylinositol-3-kinase (PI3K) pathway may be dysregulated in T-cell lymphoma. Copanlisib is a potent pan-class 1 reversible PI3K inhibitor. A phase II was performed to evaluate the efficacy and safety of copanlisib in relapsed/refractory indolent and aggressive non Hodgkin lymphomas (NHL); NCT01660451. We report here on the safety and efficacy of copanlisib in the PTCL subset from this study.
Methods: Copanlisib was administered at a dose of 0.8 mg/kg as a 1 hour infusion on days 1, 8 and 15 of a 28-day cycle. Patients continued on therapy until disease progression or unacceptable toxicity. The primary endpoint was objective response rate as assessed per independent radiologic review according to the IWS response criteria for NHL (Cheson et al., JCO 20:579, 2007). Adverse events (AE) were reported using CTCAE v4.0.
Results: A total of 17 patients with PTCL have been enrolled, with 17 patients evaluable for safety and 14 evaluable for primary efficacy assessment per protocol. Median age was 61 years (range 41-73), 65% were male and ECOG status 0/1/2 was 41%/35%/24%. Patients had received a median of 3 prior lines of therapy (range 1-6), with the median time since last systemic anti-cancer therapy being 2.5 months (range 0.3-12.1). The median treatment duration was 7.3 weeks (range 2-135). Dose modifications of any type were recorded in 9 patients (53%); 2 patients were dose reduced (to 0.6 mg/kg) and 2 patients permanently discontinued due to AEs. The most common treatment-related AEs (all grade/grade 3 and 4) were: reduced neutrophils (29.4%/23.5%), hypertension (23.5%/23.5%), hyperglycemia (17.6%/11.8%), diarrhea (23.5%/5.9%), and fatigue (17.6%/5.9 %). Amongst other AEs of interest reported here, there was one report of pneumonitis (grade 1) and no cases of colitis. There were 3 grade-5 events, one of which was related to study drug (lung infection).
The objective response rate (ORR) per independent radiologic assessment was 21.4%, with 2 complete responses (CR; 14.3%) and 1 partial response (PR; 7.1%) observed. The duration of response (including censored values) for these patients ranged from 109-786 days. An additional 5 patients had stable disease (SD; 35.7%) as best response. Per investigator assessment, the ORR was 35.7%, with 3 CRs (21.4%), one uCR (7.1%), and 1 PR (7.1%). The duration of response for these patients ranged from 55-841 days. The uCR patient went on to receive an allogeneic bone marrow transplant.
Conclusions: Copanlisib as single agent is active in relapsed/refractory PTCL, with complete responses observed. AEs related to copanlisib administration were similar to that seen in other subpopulations of the study and were manageable. Further studies, both single agent and combination, are planned in PTCL.