US-based clinical-stage biopharmaceutical company Corvus has reported positive pre-clinical and preliminary biomarker data from its ongoing Phase I/Ib trial of CPI-444, both as a single agent and combined with Genentech’s Tecentriq (atezolizumab) to treat cancer.
Corvus’ CPI-444 has been developed as an orally administered antagonist of the adenosine A2A receptor. It blocks the action of adenosine produced by tumours.
Genentech’s Tecentriq is a fully humanised, monoclonal antibody developed to target protein programmed cell death ligand 1 (PD-L1).
The first dose-escalation part of the trial was conducted in four cohorts for a period of 28 days involving 12 patients suffering from non-small-cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, colorectal cancer, head and neck cancer, bladder cancer and prostate cancer.
Three cohorts treated patients with single agent CPI-444 while one cohort administered a combination of CPI-444 and Tecentriq.
The second part of the study will test CPI-444 as a single agent, which will be administered in five disease-specific cohorts, and CPI-444 in combination with TECENTRIQ in five additional matched disease-specific cohorts.
Preclinical study results have suggested the efficacy of CPI-444, both as a single agent and in combination with anti-PD-1 and anti-PD-L1 antibodies, in triggering anti-tumour immunity and suppressing tumour progression in animal models of cancer.
After analysing patients with various solid tumours, the preliminary biomarker data demonstrated CPI-444 in blocking peripheral blood lymphocyte A2A receptors.
Pharmacodynamic markers on peripheral blood lymphocytes exhibited activation of T-cell mediated immunity in all three patients treated with CPI-444, which was also well-tolerated throughout the analysis.
Corvus oncologist, co-founder, president and CEO Richard Miller said: “We are very encouraged by the early data showing that CPI-444 is well tolerated, and by the biomarker data indicating that treatment with CPI-444 as a single agent is associated with activation of T-cells detected in the blood.
“We believe this is the first demonstration of immune modulation in cancer patients receiving an adenosine antagonist.”