On January 10, 2017 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported that the protocol-predefined criteria for expansion has been reached for the cohort of patients with renal cell carcinoma treated with single-agent CPI-444 in the Company’s ongoing Phase 1/1b study (Press release, Corvus Pharmaceuticals, JAN 10, 2017, View Source [SID1234517329]). The size of that cohort will be increased from 14 to 26 patients.

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The Phase 1/1b study is evaluating CPI-444, a selective and potent inhibitor of the adenosine A2A receptor, as a single agent and in combination with Genentech’s Tecentriq (atezolizumab),‎ a humanized monoclonal antibody targeting protein programmed cell death ligand 1 (PD-L1). The study has been enrolling patients ahead of schedule. The first part of the trial (dose-selection) was completed in October 2016, and enrollment of patients in disease-specific cohorts in the second part of the trial is currently underway.

"We are delighted with the progress of the study and encouraged by the early signs of single-agent activity in heavily pre-treated renal cell cancer patients, some of whom were refractory to prior therapy with an anti-PD1 antibody," said Richard A. Miller, an oncologist and co-founder, president and chief executive officer of Corvus. "If these findings are confirmed with longer follow up and a larger set of patients, we could potentially initiate a registration trial before the end of 2017. That study would evaluate CPI-444 in late-stage renal cancer patients, for whom current treatment options are very limited."

The protocol-predefined criteria for expansion is the finding of a response (defined as a complete response, partial response or stable disease) in at least one patient in the disease-specific cohort of 14 patients with renal cell cancer. In the initial four patients treated with single agent CPI-444 (in either the dose-selection or disease-specific cohorts), one patient, refractory to prior treatment with anti-PD1, achieved a partial response, two have stable disease, and one has shown tumor progression. A fifth patient (in the dose-selection cohort), refractory to prior treatment with anti-PD1, received CPI-444 in combination with Tecentriq (atezolizumab),‎ and has stable disease. Four of the five patients remain on treatment, with two receiving treatment for more than 30 weeks. All patients had previously failed approved therapies. To date, CPI-444 has been well tolerated when given orally twice daily.

Dr. Miller added, "We have also seen promising evidence of single-agent activity in patients in other disease-specific cohorts, including lung cancer and melanoma. Overall, in 33 patients receiving single agent CPI-444, we have seen 2 partial responses and 12 patients with stable disease. We are collecting data from these cohorts and hope to expand the size of these cohorts in the future."

TRIAL DESIGN
The Phase 1/1b trial is designed to examine the activity of CPI-444 as a single agent and in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 antibody. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, MSI-H colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed all standard therapies are eligible. The primary endpoints of the study are response rate and duration of clinical benefit (defined as complete response, partial response or stable disease). Patients are treated until disease progression or evidence of grade 3 or 4 toxicity.

The dose-selection part of the study included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with Tecentriq (atezolizumab‎). A treatment cycle is 28 days. Based on biomarker analyses showing sustained, complete blockade of the adenosine A2A receptor in peripheral blood lymphocytes, and evidence of immune activation in circulating lymphocytes, an optimum single agent and combination dose of 100 mg twice a day for 28 days was selected for the second part of the study. As defined in the protocol, patients in the dose-selection stage of the trial receiving the dose and schedule selected for evaluation in the second part of the study are included in the disease-specific cohort efficacy analysis.

The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts (renal cell, lung, triple-negative breast, melanoma and a category of ‘other’ that includes bladder, MSI-H colorectal cancer and prostate cancer) and CPI-444 in combination with Tecentriq (atezolizumab),‎ in five additional matched disease-specific cohorts. Each of the 10 cohorts is initially enrolling 14 patients but may be expanded based on efficacy as has occurred with the single-agent cohort of patients with renal cell cancer.