Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma

Ann Oncol. 2017 Sep 1;28(9):2169-2178. doi: 10.1093/annonc/mdx289.


Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase 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 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 phosphatidylinositol 3-kinase 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. This trial is registered with number NCT01660451 (Part A).

Keywords: PI3K inhibitor; copanlisib; malignant lymphoma; treatment.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Recurrence
  • Survival Analysis


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyrimidines
  • Quinazolines
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • copanlisib

Associated data