ChemoCentryx, Inc. announced the presentation of preclinical data and initial pharmacokinetic (PK) and pharmacodynamic data from the ongoing Phase I clinical study of CCX559 during a poster session at the American Association for Cancer Research Annual Meeting 2022. The PD-L1/PD-1 interaction is one of the major immune checkpoints that limits the ability of effector T cells to destroy cancer cells. As a potential next generation therapy, an orally administered small molecule inhibitor of PD-L1 could have advantageous properties compared to approved monoclonal antibodies, such as better penetration into solid tumors, reduced immunogenicity, lack of Fc-mediated side effects and convenience of oral administration.

Preclinical characterization has demonstrated that CCX559 is a potent inhibitor of PD-L1 that blocks binding to PD-1 and CD80 and prevents PD-L1 inhibition of T cell activation. During 2021, ChemoCentryx initiated a first-in-human Phase I dose escalation study to evaluate the safety, tolerability, PK and PD of CCX559 in patients with various types of advanced cancer. In this Phase I basket study, CCX559 is taken orally once per day at specified dose levels, starting at 30 mg and ranging to date to 120 mg.

In the AACR poster titled, CCX559, an orally administered small molecule PD-L1 inhibitor for the treatment of solid tumors: Initial Pharmacokinetic and Pharmacodynamic Results from the in Progress First-In-Human Trial, ChemoCentryx reported initial data available to date from patients enrolled in the first three dose cohorts in the ongoing Phase I study. Patients received CCX559 once daily at doses of 30 mg, 60 mg and 120 mg. All patients receiving 120 mg of CCX559 were included in the PK evaluation reported in the poster.

PD data for seven of the 120 mg patients were also presented. PK evaluation shows human CCX559 exposure is in line with preclinical projections. The mean exposure at 120 mg CCX559 in patients is comparable to exposures with anti-tumor activity in preclinical models and sufficient for PD-L1 target coverage, the half-life of the drug was also in line with projections.

PD activity results from the first cycle of treatment indicate that CCX559 is immunomodulatory. CD4 and CD8 T cell proliferation increased in all dose groups; soluble PD-L1 levels in plasma were significantly increased in the 120 mg patients by the end of the first cycle of dosing; and plasma IFN?, CXCL9, CXCL10 were increased in the majority of patients assessed at 120 mg. The PD activity of CCX559 is consistent with approved antibody inhibitors of PD-L1, in the extent and kinetics of the observed Th1 responses.

ChemoCentryx expects to present additional findings from this ongoing Phase I study at major oncology conferences through 2022. During the second half of 2022, the Company plans to advance CCX559 into a Phase Ib/II clinical trial to measure anti-tumor effects of CCX559 more directly.