Corvus Pharmaceuticals, Inc. announced new data for CPI-818, the Company's ITK inhibitor, demonstrating the potential to treat a variety of solid and hematological cancers based on a novel immunotherapy mechanism of action. The data includes updated interim results from the CPI-818 Phase 1/1b clinical trial that continues to demonstrate the potential of ITK inhibition and the absolute lymphocyte count (ALC) biomarker in T cell lymphoma (TCL). The data is being presented in a poster at the International Conference on Malignant Lymphoma (ICML) meeting, which is taking place June 13-17, 2023 in Lugano, Switzerland.

CPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. Corvus recently incorporated a minimum ALC as an eligibility criterion for enrollment in the clinical trial. Based on the current enrollment rate of the Phase 1/1b clinical trial, Corvus believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registrational Phase 3 randomized clinical trial.

As recommended by the FDA, Corvus plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place during the third quarter of this year. Updated interim data as of May 18, 2023 (waterfall plot shown below): A total of 30 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose, including 20 evaluable for tumor response. There were 3 complete responses (CR) and 3 partial responses (PR) with one of these PRs demonstrating continued regression of the tumor.

One of the patients with a CR and 2 with PRs remained on therapy. A total of ten patients remained on therapy, including six who have not had their initial tumor response evaluation. For patients with ALC above 900 per cubic milliliter of blood, objective responses (CR plus PR) were seen in 6 of 14 patients with disease control (CR, PR and stable disease) in 12 of 14 patients.

No objective responses were seen in six patients (0 for 6) with ALC below 900. Updated interim data as of May 18, 2023: In one TCL patient treated with CPI-818 for which serial tumor biopsy samples could readily be obtained, single cell RNA sequencing from paired samples comparing baseline and on-treatment specimens showed an increase in tumor infiltrating CD8+ T cells; an increase in cytolytic effector molecules such as granzymes and perforin in the T cells; and an increase in T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells. In addition, flow cytometry analysis of paired blood samples comparing baseline and on treatment revealed a similar finding in both CD8 T cells and CD4 T cells.

These results are consistent with preclinical data described below and support the novel immunotherapy mechanism of action of selective ITK inhibition, which is based on Th1 skewing and the resulting shift in immune response to eliminating cancer cells. Additional laboratory findings indicated that treatment with CPI-818 induces a reversal of T cells expressing exhaustion markers. T cell exhaustion is a known mechanism of resistance to checkpoint inhibitor therapy.