Corvus Pharmaceuticals is expanding the number of patients with renal cell carcinoma receiving the adenosine A2A receptor inhibitor, CPI-444, as monotherapy in the ongoing Phase 1/1b trial assessing CPI-444 alone or in combination with Tecentriq (atezolizumab).
The predefined criteria for expansion was stable disease or better in at least one patient in the disease-specific cohort. Among the initial four patients with renal cell carcinoma treated with CPI-444 monotherapy, one achieved a partial response and two reached stable disease. This group will grow to 26 patients from its original 14.
“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,” Richard A. Miller, an oncologist, and co-founder, president and chief executive officer of Corvus, said in a news release. “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 open-label, multicenter, dose-selection Phase 1/1b study (NCT02655822) was designed to examine the activity of CPI-444 as a single agent and in combination with the anti-PD-L1 Tecentriq in patients with solid tumors who failed all standard therapies. Patients with non-small cell lung cancer, triple-negative breast cancer, prostate cancer, melanoma, colorectal cancer, renal cell cancer, and bladder cancer, are eligible.
In the study’s first part, the dose-selection part, researchers sought to assess the optimum dose and treatment regimen for CPI-444 alone or in combination with Tecentriq. Four cohorts of 12 patients each were included; three of these groups were treated with CPI-444 as a single agent in 28-day cycles (100 mg twice daily for the first 14 days, 100 mg twice daily for 28 days, and 200 mg once daily for the first 14 days), and one was treated with CPI-444 (50 mg or 100 mg twice daily for the first 14 days) plus Tecentriq.
Based on data from each cohort, including immune cell activation, an optimum dose of 100 mg twice a day for 28 days was selected for the second part of the study, both in single agent and combination cohorts.
In this second part, patients in the dose-selection stage were divided in disease-specific cohorts. The study included five groups receiving CPI-444 as monotherapy — melanoma, renal cell, lung, and triple-negative breast cancer, plus an “other” category of bladder, colorectal, and prostate cancer patients. The combination of CPI-444 with Tecentriq is being evaluated in five additional cohorts for the same diseases.
Each cohort initially recruited 14 participants, but it was at this stage that three patients in the renal cell cancer cohort responded to the monotherapy, allowing more of these patients to be enrolled.
“We have also seen promising evidence of single-agent activity in patients in other disease-specific cohorts, including lung cancer and melanoma,” Miller added. “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.”
The trial is taking place at 33 sites in the United States, Australia and Canada; more information, including enrollment information, is available on its clinical trials.gov webpage.