Clinical and laboratory results support a new immuno-oncology approach with CPI-006
via activation of immune cells and the inhibition of adenosine production
Initial Results demonstrated dose-dependent disease control in patients with advanced, refractory disease
when administered as a monotherapy and in combination with ciforadenant (CPI-444)
Company to host investor and analyst reception today at 6:00 pm CT
BURLINGAME, Calif., June 02, 2019 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, today announced initial results from its Phase 1/1b trial of CPI-006, the Company’s anti-CD73 antibody. The initial clinical data from the dose escalation study showed a trend toward longer disease control with higher doses of CPI-006, and enhanced disease control with CPI-006 in combination with ciforadenant (CPI-444) compared with monotherapy, in patients with advanced, refractory cancer. The initial results were presented today in an oral session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago by Jason J. Luke, M.D., principal investigator of the trial and Director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center and Associate Professor of Medicine at the University of Pittsburgh School of Medicine.
“We selected CPI-006 for development because it possesses unique properties,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “These data demonstrate that the binding of CPI-006 to CD73 induced activation of various immune cells, which is independent of adenosine, and that CPI-006 also inhibited production of adenosine. We are not aware of any other agent targeting CD73 that has exhibited these properties. We now have two agents, CPI-006 and ciforadenant, that target different components of the adenosine pathway, with CPI-006 having the potential to stimulate immune responses. Our initial results from the CPI-006 Phase 1/1b study, show biologic activity even at the lowest doses administered, a trend toward longer disease control with higher doses, and enhancement when used in combination with ciforadenant.”
The CPI-006 Phase 1/1b study is currently enrolling patients with a variety of cancers who have failed standard therapies. It 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 ciforadenant (CPI-444), a selective and potent inhibitor of the adenosine A2A receptor; and in combination with pembrolizumab, an anti-PD-1 antibody. The efficacy endpoints are complete response (CR), partial response (PR), disease control rate, duration of response, progression-free survival and overall survival.
Initial Phase 1/1b Results Presented at ASCO 2019
Dr. Luke presented initial results from the first two arms of the study, which are evaluating CPI-006 as a single agent and in combination with ciforadenant. The presentation included data from 12 patients who received CPI-006 given intravenously as monotherapy (at doses of 1, 3, 6 or 12 mg/kg every 21 days) and eight patients who received the combination treatment of CPI-006 (1, 3 or 6 mg/kg every 21 days plus a fixed dose of ciforadenant 100 mg twice daily). These patients had advanced, refractory disease (four had colorectal cancer, four had pancreatic cancer, four had prostate cancer, three had head and neck cancer, three had renal cell cancer, one had bladder cancer and one had sarcoma), and had failed a median of four prior therapies. The key highlights from the initial CPI-006 clinical results include:
- Pharmacokinetic studies showed a dose-dependent increase in CPI-006 plasma exposure, with doses of 12 mg/kg achieving complete and sustained occupancy of CD73 on peripheral blood lymphocytes.
- Biopsies revealed penetration of CPI-006 and occupancy of CD73 in tumors at doses of 12 mg/kg.
- Infusions of CPI-006 resulted in rapid activation and migration of B lymphocytes with concomitant changes in peripheral blood CD4 to CD8 ratios. These changes are believed to be consistent with trafficking and activation of antigen presenting cells to peripheral lymph nodes. In vitro and in vivo studies revealed increased expression of the activation markers CD69, CD83 and CD25, as well as increases in CD86 and class II MHC (major histocompatibility complex) indicating activation of antigen presenting cells, such as B cells, macrophages and dendritic cells.
- A patient with metastatic prostate cancer that had previously failed multiple anti-androgen therapies and chemotherapy received over 11 cycles (a cycle equals 21 days) of CPI-006 monotherapy at a dose of 6 mg/kg and showed reduction in tumor volume and a reduction in bone pain.
- A trend toward longer disease control was seen in patients treated with doses of 6 mg/kg and higher, doses which achieved sustained target occupancy; combination therapy appeared to enhance disease control.
- For all dose cohorts of monotherapy, four patients had stable disease (two pancreatic, one prostate and one colorectal cancer). No patients receiving 1mg/kg of monotherapy achieved stable disease; all of these patients had disease progression at first evaluation. For the ciforadenant combination cohorts, the follow up period was short; two patients (one pancreatic and one prostate) have stable disease at the lowest dose of 1 mg/kg. Five patients (two monotherapy and three combination) continue on therapy with follow-up of 2-11 treatment cycles.
- CPI-006 was well tolerated at all dose levels, with no dose-limiting toxicities. Grade 1 infusion reactions were detected (N=3 patients) and mitigated with premedication with acetaminophen and antihistamine. Grade 3 or 4 toxicities included a grade 3 anemia (N=1).
“These initial Phase 1/1b study results highlight a potentially new approach to immunotherapy and are very encouraging, with signs of tumor control and regression occurring in patients with very advanced cancers who are resistant to current treatment approaches,” said Dr. Luke.
ASCO Investor and Analyst Reception
Corvus will host an investor and analyst reception today, June 2, 2019, at 6:00 pm CT, to discuss the CPI-006 data presented at ASCO 2019. The reception will feature Dr. Luke, Dr. Miller, and Mehrdad Mobasher, M.D., M.P.H, vice president and chief medical officer of Corvus. The company will offer a live webcast of the reception, which can be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus' website for one year.
CPI-006 is a potent humanized monoclonal antibody that reacts with a unique epitope on CD73 including the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of activating lymphocytes and antigen presenting cells and of inhibiting the production of adenosine.
Ciforadenant (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.
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies. Corvus’ lead product candidate, ciforadenant (CPI-444), a small molecule inhibitor of the A2A receptor, is currently being evaluated in a multicenter amended Phase 1b/2 clinical trial in patients with various solid tumors. This successive expansion cohort trial is examining the activity of ciforadenant both as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody. Corvus is conducting the trial with Genentech, a member of the Roche Group, under a clinical trial collaboration the two companies entered into in October 2015. In May 2017, Corvus and Genentech expanded the collaboration and are now conducting a trial of ciforadenant and atezolizumab in patients with non-small cell lung cancer (NSCLC) who have failed prior therapies with anti-PD-(L)1 and platinum-based chemotherapy. Corvus is evaluating two additional product candidates: CPI-006, a humanized monoclonal antibody directed against CD73, in a multicenter Phase 1/1b clinical trial in patients with various solid tumors, and CPI-818, an oral, small molecule drug that has been shown to selectively inhibit ITK, in a multicenter Phase 1/1b clinical trial in patients with several types of T-cell lymphomas. For more information, visit www.corvuspharma.com.
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-006 and ciforadenant, 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 potential timing and availability of data from the Company’s ongoing clinical trials. 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2019, filed with the Securities and Exchange Commission on May 9, 2019, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the accuracy of the Company’s estimates relating to its ability to initiate and/or complete clinical trials; the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of CPI-006 and ciforadenant; the results of preclinical studies may not be predictive of future results; the unpredictability of the regulatory process; regulatory developments in the United States and foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
Chief Financial Officer
Corvus Pharmaceuticals, Inc.