389P - Biomarker and clinical activity of CPI-444, a novel small molecule inhibitor of A2A receptor (A2AR), in a Ph1b study in advanced cancers

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical research
Translational Research
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Ian McCaffery
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors I. McCaffery1, G. Laport2, A. Hotson1, S. Willingham1, A. Patnaik3, M. Beeram3, R. Miller2
  • 1Translational Sciences, Corvus Pharmaceuticals, 94010 - Burlingame/US
  • 2Clinical Development, Corvus Pharmaceuticals, 94010 - Burlingame/US
  • 3The Start Center For Cancer Care, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US

Abstract

Background

Adenosine is immunosuppressive and is produced at high concentrations in tumors by both CD73 and direct release from tumor cells. Adenosine activates A2AR, an immune checkpoint that leads to direct suppression of effector T cells and stimulation of regulatory T cells. CPI-444 is an oral, selective A2AR inhibitor that has been well tolerated in Ph 1 and 2 studies in non-oncology indications. CPI-444 shows activity in multiple preclinical tumor models as a single agent and synergistic efficacy when given in combination with other checkpoint inhibitors, including anti-PD-L1.

Methods

CPI-444, with or without the investigational agent atezolizumab (anti-PD-L1), is being studied in an ongoing Ph1b trial in solid tumor patients (pts). Pts with either lung, melanoma, triple negative breast, bladder, colorectal, renal, or head and neck cancers are treated at various doses of either single agent CPI-444 or combined with atezolizumab. After a dose selection stage, pts are treated in 10 disease specific cohorts (5 single agent and 5 combination). Cohorts may be expanded based on response criteria: complete response, partial response or stable disease (SD). Biomarkers are evaluated including immune cells by flow cytometry in peripheral blood and pre/post treatment tumor biopsies as well as adenosine pathway modulation by immunohistochemistry and gene expression.

Results

In 7 pts treated to date, CPI-444 has been well tolerated with no Grade 3 or 4 treatment related adverse events. 2 pts (1 combination and 1 single agent) have reached the first efficacy assessment by CT and both demonstrated SD (unconfirmed at 2 months); these 2 pts, and 4 others who have not yet reached efficacy evaluation, remain on treatment. In the two pts with SD, peripheral blood showed increases in PD-1 + CD8+ cells (1.7 and 2.4 fold compared to baseline). This is consistent with preclinical models and reflect effector T cell activation, similar to reports by others in patients treated with anti-PD-L1.

Conclusions

CPI-444 is well tolerated and demonstrates biological activity indicating activation of T cell immunity. This is the first demonstration of treatment-associated immune modulation in cancer patients receiving an adenosine antagonist.

Clinical trial identification

ClinicalTrials.gov Identifier:NCT02655822 Phase 1/1b Study to Evaluate the Safety and Tolerability of CPI-444 Alone and in Combination With Atezolizumab in Advanced Cancers

Legal entity responsible for the study

Corvus Pharmaceuticals

Funding

Corvus Pharmaceuticals

Disclosure

I. McCaffery, G. Laport, A. Hotson, S. Willingham: Employee and stockholder of Corvus Pharmaceuticals A. Patnaik, M. Beeram: Research support to institution from Corvus Pharmaceuticals R. Miller: Employee, Director and Stockholder of Corvus Pharmaceuticals