1001PD - Tumor gene expression signatures of BCR/PI3K dependence in association with copanlisib monotherapy activity in heavily pretreated patients with ind...

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Lymphomas
Haematologic Malignancies
Presenter Li Liu
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors L. Liu1, K. Köchert2, H. Seidel3, J. Garcia-Vargas4, B.H. Childs5, G. Follows6, K. Bouabdallah7, M. Dreyling8, C. Peña1
  • 1Biomarker Strategy, Bayer HealthCare Pharmaceuticals, 07981 - Whippany/US
  • 2Clinical Statistics, Bayer AG, Berlin/DE
  • 3Bioinformatics, Bayer AG, Berlin/DE
  • 4Clinical Development, Bayer HealthCare Pharmaceuticals USA, 07981 - Whippany/US
  • 5Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 6Department Of Haematology, Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital, Cambridge/GB
  • 7Service D'hématologie Et De Thérapie Cellulaire, University Hospital of Bordeaux, Pessac/FR
  • 8Medizinische Klinik Und Poliklinik Iii, Klinikum der Universität München-Grosshadern, Munich/DE



Copanlisib, a novel class I PI3K inhibitor with predominant activity against α and δ isoforms, has shown robust single agent anti-tumor activity in a phase 2 study in heavily pretreated patients with indolent NHL (iNHL) and follicular lymphoma (FL) (NCT01660451; Part B), with response rates of 59.6% and 58.7%, respectively. Baseline tumor gene expression profiling (GEP) was performed to confirm if gene signatures identified in patients with indolent or aggressive NHL (NCT01660451; Part A) are molecular determinants for copanlisib antitumor activity in Part B.


Signaling pathway gene sets (n = 33) were ranked by enrichment analysis (GSEA) for association with objective response based on normalized enrichment score (NES) and false discovery rate (FDR) q values. The association of weighted gene-expression score (WGS, reflecting the overall expression level for each gene set) with response was analyzed by logistic regression.


Seventy-one patients with iNHL, including 54 FL, had both response data and evaluable gene expression data. All 5 gene sets reflecting upregulated PI3K/BCR signaling were top-ranked for association with higher response rates in iNHL (GSEA NES ≥ 1.93, FDR q 


Tumor gene expression profiling demonstrates that up-regulation of the BCR/PI3K pathway is frequent and dominant in iNHL and FL, and is associated with the high and durable copanlisib responses. These findings are consistent with copanlisib’s mode of action and strongly support the rationale for treatment of iNHL and FL patients with copanlisib.

Clinical trial identification

NCT01660451; Part B

Legal entity responsible for the study

Bayer AG


Bayer AG


L. Liu: Employee: Bayer HealthCare Pharmaceuticals. K. Köchert, H. Seidel: Employee: Bayer AG. J. Garcia-Vargas, B.H. Childs, C. Peña: Employment: Bayer HealthCare Pharmaceuticals. All other authors have declared no conflicts of interest.