Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3212 - PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Ahmad Awada

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

A.H. Awada1, F. Morschhauser2, J. Machiels3, G. Salles4, S. Rottey5, S. Rule6, D. Cunningham7, F. Peyrade8, C. Fruchart9, H. Arkenau10, I. Genvresse11, K. Koechert11, G. Cisternas12, C. Granvil13, C. Pena14, L. Liu14

Author affiliations

  • 1 Department Of Medicine, Institute Jules Bordet, 1000 - Brussels/BE
  • 2 Department Of Hematology, CHRU - Hôpital Claude Huriez, Lille/FR
  • 3 Oncology, Cliniques Universitaires St. Luc, 1200 - Brussels/BE
  • 4 Department Of Hematology, Civil Hospices of Lyon, University Claude Bernard Lyon-1, Pierre Benite/FR
  • 5 Department Of Medical Oncology, Gent University Hospital, 9000 - Gent/BE
  • 6 Department Of Haematology, Plymouth University, PL4 8AA - Plymouth/GB
  • 7 Medicine, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 8 Medical Oncology, Centre Anticancer Antoine Lacassagne, 6100 - Nice/FR
  • 9 Department Of Clinical Hematology, Centre Francois Baclesse, 14076 - Caen/FR
  • 10 Scri, Sarah Cannon Research Institute SCRI UK, W1G 6AD - London/GB
  • 11 Pharmaceutical Division, Bayer AG, Berlin/DE
  • 12 Oncology, Bayer AG, 13353 - Berlin/DE
  • 13 Clinical Pharmacology, Bayer HealthCare Pharmaceuticals Inc, Whippany/US
  • 14 Clinical Science, Bayer HealthCare Pharmaceuticals Inc, Whippany/US
More

Resources

Abstract 3212

Background

Copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant activity against α and δ isoforms, shows immune stimulating effects and anti-tumor activity in combination with immune checkpoint blockers in tumor models. Here we explore tumor PI3K signaling and the effects of copanlisib on immune and tumor microenvironment modulation in subjects with NHL and solid tumors (ST) in a phase I pharmacodynamic study (NCT02155582).

Methods

Patients received 0.4 or 0.8 mg/kg (equivalent to a flat dose of 60 mg) copanlisib on an intermittent schedule (QW, IV, 3 wks on/1 wk off). Tumor biopsies were performed at baseline and Day 15. Tumor PI3K isoforms, PTEN, and CD3, CD4 and CD8 tumor infiltrating lymphocytes (TILs) were assessed by IHC. Plasma protein markers were measured using multiplexed immunoassay. Tumor and lymphoma responses were based on RECIST 1.1 and modified Cheson 2007 criteria, respectively.

Results

A total of 61 patients were treated: 33 NHL (20 at 0.4 mg/kg and 13 at 0.8 mg/kg) and 28 ST (14 at 0.4 mg/kg and 14 at 0.8 mg/kg). Among patients treated at 0.8 mg/kg, 2 had CR (PTCL and DLBCL) and 5 had PR (MCL, FL, 2 DLBCL, and endometrial adenocarcinoma); 1 additional PR (DLBCL) occurred at 0.4 mg/kg. Tumor PI3K α was detected in most NHL (18/19) and ST (22/25) samples with comparable intensity. PI3K δ was predominantly present in NHL (18/19). PI3K ß and γ were present in a subset of NHL and ST. PTEN loss was more frequent in ST than NHL. CD3, CD4 and CD8 TIL numbers were higher in NHL than in ST. At 0.8 mg/kg copanlisib decreased tumor pAKT and pS6 in both NHL and ST, and reduced CD4 TILs in NHL (mean -81%, n = 7), with little effect on CD8 TILs in both NHL and ST. In plasma, copanlisib decreased cytokine/chemokines (e.g. CCL2, CCL5, CCL17), and factors associated with macrophages (e.g. CD163, CCL4, CCL22) and Treg cells (IL-2Ra). High baseline levels of CD27 and IL2Ra were associated with tumor reduction in NHL (p < 0.05, unadjusted).

Conclusions

The high prevalence of the PI3K isoforms – especially α in both NHL and ST and δ in NHL – is consistent with a role for PI3K signaling in immune suppression. The immune modulation profile for copanlisib supports combination studies with immunotherapy.

Clinical trial identification

NCT02155582.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Editorial Acknowledgement

Disclosure

I. Genvresse, K. Koechert, G. Cisternas, C. Granvil, C. Pena, L. Liu: Employee: Bayer. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings