208O_PR - CRS-207 with chemotherapy (chemo) in malignant pleural mesothelioma (MPM): Results from a phase 1b trial

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Multidisciplinary management of thoracic malignancies
Topics Cytotoxic agents
Mesothelioma
Therapy
Biological therapy
Presenter Thierry Jahan
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors T. Jahan1, R. Hassan2, E. Alley3, H. Kindler4, S. Antonia5, L. Coussens6, C. Whiting7, A.L. Murphy7, A. Thomas2, D.G. Brockstedt7
  • 1Department Of Medicine, Division Of Hematology Oncology, University of California San Francisco UCSF, 94143 - San Francisco/US
  • 2Thoracic And Gi Oncology Branch, National Cancer Institute, Bethesda/US
  • 3Division Of Hematology/oncology, University of Pennsylvania, Philadelphia/US
  • 4Gastrointestinal Oncology And Mesothelioma Programs, Section Of Hematology/oncology, University of Chicago, Chicago/US
  • 5Department Of Thoracic Oncology, H Lee Moffitt Cancer Center, Tampa/US
  • 6Cell, Developmental & Cancer Biology Department, Oregon Health & Science University, Portland/US
  • 7Clinical And Research Development, Aduro Biotech, Inc., Berkeley/US

Abstract

Background

MPM is an aggressive disease with poor prognosis. CRS-207 is live, attenuated, double-deleted Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin, activating innate and adaptive immunity. The combination of CRS-207 and chemo may act synergistically to alter the tumor microenvironment to potentiate immune-mediated killing.

Methods

Eligible patients (pts) were chemo-naïve with unresectable MPM, ECOG 0–1, and adequate organ function. Patients received 2 CRS-207 infusions (1×109 CFU) 2 weeks apart, 6 cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) 3 weeks apart, followed by 2 additional CRS-207 infusions 3 weeks apart. Eligible patients received maintenance CRS-207 every 8 weeks; all patients were followed every 8 weeks until disease progression. Study objectives include safety, immunogenicity, tumor response and tumor marker kinetics. Immune analyses included multiplexed immunohistochemistry (IHC) of tumor-infiltrating lymphocytes (TILs), flow cytometry analysis of peripheral blood mononuclear cells, and Luminex analysis of serum biomarkers.

Results

As of August 2015, 38 pts have been enrolled. The most commonly reported CRS-207-related adverse events include grades 1/2 infusion-related fever, chills/rigors, hypotension and nausea/vomiting with no treatment-related serious adverse events or deaths. Of evaluable pts, 59% (20/34) had partial response post-treatment and 35% (12/34) had stable disease for overall 94% disease control rate. Median progression-free survival (PFS) was 8.5 months (mos); median overall survival had not been reached. IHC data from 3 patients revealed an increase in TILs post-CRS-207. Treatment-associated changes in circulating immune cells and biomarkers were also observed.

Conclusions

CRS-207 has been well tolerated and in combination with chemo showed encouraging anti-tumor activity with 59% response rate and median PFS of 8.5 mos. Recruitment and expansion of TILs and changes in circulating immune cells and serum biomarkers were observed post-CRS-207. These results appear considerably better than those expected with chemo alone and will be evaluated in a Phase 3 trial.

Clinical trial identification

NCT01675765

Legal entity responsible for the study

Aduro Biotech, Inc.

Funding

Aduro Biotech, Inc.

Disclosure

T. Jahan: Member of Aduro Mesothelioma Steering Committee. R. Hassan, E. Alley, H. Kindler: Member of Aduro Steering Committee. C. Whiting, A.L. Murphy, D.G. Brockstedt: Aduro stock owner. All other authors have declared no conflicts of interest.