Corvus Pharmaceuticals Announces Initiation of Phase 1/1b Clinical Trial of Investigational Anti-CD73 Antibody, CPI-006, in Patients with Advanced Cancer
“CPI-006 is an antibody engineered to completely inhibit the CD73 enzyme by binding to its active site. We look forward to evaluating this anti-CD73 antibody in our comprehensive Phase 1/1b trial, which we believe is the first human clinical trial in oncology to evaluate the effect of dual-blockade of the adenosine pathway by inhibiting both CD73 and the A2A receptor,” said
About the Phase 1/1b Trial Design
The Phase 1/1b trial is designed to select the dose and evaluate the safety, pharmacokinetics, immune biomarkers and efficacy of CPI-006 as a single agent, in combination with CPI-444 and in combination with pembrolizumab. Patients with non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and other cancers who have failed standard therapies are eligible. The efficacy endpoints are complete response (CR), partial response (PR), disease control rate, duration of response, progression-free survival and overall survival.
In the dose-selection part of the trial, doses of CPI-006 will be escalated in the single-agent arm and in the two combination arms to determine the maximally tolerated dose or the dose that saturates the CD73 enzyme. Fixed doses of CPI-444 and pembrolizumab will be used. Once an optimum dose of CPI-006 is determined, the second part of the trial will enroll patients in nine cohorts: three will receive CPI-006 alone, three will receive CPI-006 in combination with CPI-444, and three will receive CPI-006 with pembrolizumab. Patients with NSCLC, RCC and the group of other cancers will be enrolled into each of the three disease-specific arms. Each of the nine cohorts may initially enroll up to 11 patients. However, if there is one or more objective responses (CR or PR) in the 11 patients, the cohort may be expanded to 28 patients. The trial may enroll up to 350 patients in total.
About CD73 and Adenosine
CD73 is a cell surface enzyme whose function is to convert adenosine monophosphate (AMP) to adenosine by removing phosphate from AMP. CD73 is expressed on cells of the immune system, including T-cells and B-cells. CD73 is also present on many tumors, including lung, renal, melanoma, colon, prostate, breast and others. In the tumor microenvironment, CD73 produces adenosine, which binds to the adenosine A2A receptor on immune cells and inhibits various immune responses including those directed against the tumor. Tumors utilize this immunosuppressive mechanism to escape attack by the immune system.
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme.
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company’s anti-CD73 antibody, CPI-006, both as a single agent and in combination with CPI-444 and pembrolizumab, the Company’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1/1b clinical trial of CPI-006, and the Company’s Phase 1/1b clinical trial of CPI-444. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Annual Report on Form 10-K for the year ended
Director, Business Development