Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma
Mené sur 33 patients atteints d'un lymphome de type indolent et sur 51 patients atteints d'un lymphome aggressif récidivant ou réfractaire, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité du copanlisib, un inhibiteur de PI3K dispensé par voie intraveineuse
Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant activity against the
α- and δ- isoforms. Patients and methods: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. Results: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 weeks and 8 weeks in the indolent and aggressive cohorts, respectively (overall range, 2
–138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range, 0–874) and 70 days (range, 0–897), respectively; median duration of response was 390 days (range, 0–825) and 166 days (range, 0–786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated PI3K pathway gene expression. Conclusion: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing.