China-based Angel Pharmaceuticals Ltd announced the latest results of the global Phase I/Ib clinical study for CPI-818, a first-in-class ITK inhibitor co-developed by US partner Corvus Pharmaceuticals, at the American Society of Hematology (ASH) 2022 annual meeting. The study has shown the anti-tumor activities in T-cell lymphoma (TCL), alongside therapeutic potential in Th2 and Th17-mediated autoimmune and allergic diseases.
Study Enrollment and Dosing
As of September 2, 2022, 43 patients were enrolled to receive CPI-818 twice daily at doses of 100, 200, 400, and 600 mg respectively. The plasma drug concentration provided by the 200 mg dose achieved the best effect of influencing the differentiation of T cells in vitro, and accordingly caused the most frequent and lasting tumor response in vivo, so it was selected as the best dose.
Interim Data and Responses
The interim data of TCL patients showed that 4 of the 11 patients who had received 3 lines of previous treatment had an overall objective response (ORR). One patient with peripheral T-cell lymphoma (PTCL) achieved complete remission (CR) lasting for 25 months. A patient with cutaneous T-cell lymphoma had lymph node CR for 19 months.
Immunity-Related Data
The interim data related to immunity showed that the optimal dose of 200 mg could induce Th1 deflection and block Th2 and Th17. In a patient with a large abdominal wall tumor significantly reduced, blood analysis showed that blood Th1 increased, blood Th17 decreased, and eosinophil count and IL-5 secretion decreased, consistent with the Th1 deflection and Th2 blockade. In the tumor samples of this patient, the terminally differentiated T-effector memory cells (TEMRA cells) increased. Two patients with partial remission (PR) and one patient with stable disease (SD) showed an increase in Th1 and CD8+TEMRA cells.
CPI-818 Mechanism and Safety
CPI-818, an oral IL2 inducible T-cell kinase (ITK) inhibitor, is highly selective and can play its role without affecting the proliferation of normal T cells and immune response. ITK is a non-receptor tyrosine kinase, which is expressed in T cells, NKT cells, and mast cells, and plays a key role in regulating T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR mediated signal pathways. Preliminary data suggest that CPI-818 has good safety and tolerability.
Angel Pharma Background
Angel Pharma was launched in China with the completion of a Series A financing round in October 2020, alongside a partnership with CRVS, which granted the firm Greater China rights to its CPI-818, anti-CD73 mAb CPI-006, and A2A antagonist CPI-444, as well as global commercialization and patent rights to its next-generation BTK inhibitor.-Fineline Info & Tech
