CStone Pharmaceuticals announced that the global multi-regional phase 3 registrational trial of the anti-PD-1 antibody nofazinlimab (CS1003) in combination with lenvatinib as first-line treatment for patients with advanced hepatocellular carcinoma (HCC), CS1003-305, has successfully reached its prespecified enrollment target. CS1003-305 is an international, multi-center, double-blind, randomized, phase 3 registrational clinical trial to evaluate the efficacy and safety of nofazilimab in combination with lenvatinib compared with placebo in combination with lenvatinib in subjects with no prior systemic treatment and with unresectable advanced HCC. The trial is conducted in 74 study sites globally including China, US, Spain, Italy, and Poland.

The primary endpoints are overall survival (OS) and progression-free survival (PFS). Dr. Jia Fan, academician of Chinese Academy of Sciences (CAS) and president of Zhongshan Hospital affiliated to Fudan University, is the global principal investigator for this trial. The CS1003-305 trial design was based on the encouraging data from the CS1003-102 trial.

CS1003-102 [1](NCT03809767) is a phase Ia/Ib, open-label, dose-escalation and expansion study conducted in China, arm 5 of phase 1b part which aimed to evaluate the safety and efficacy of nofazinlimab in combination with lenvatinib as first-line treatment for patients with unresectable HCC (uHCC). The primary endpoint is objective response rate (ORR) per RECIST V1.1 by investigators. As of June 22, 2020, 20 patients were enrolled and received study treatment.

The majority of patients were male (90%), had ECOG PS score 1 (75%), had BCLC stage C HCC (90%), and had HBV infection (65%). Nofazinlimab in combination with lenvatinib showed promising efficacy and manageable safety profile: A total of 20 pts were enrolled for evaluating preliminary anti-tumor activity, and the ORR reached 40% (8/20). Median follow-up duration was 6.2 months, and median PFS was 8.4 months.

Median OS and duration of response (DoR) were not reached as of the data cut-off date. A total of 20 patients were evaluable for safety assessment. The most common treatment-related adverse events (TRAEs) of any grade were blood bilirubin increased, protein urine present, and proteinuria.

5 patients each had a grade 3 TRAE, including hypertension, bilirubin conjugated increased, diarrhea, diabetes mellitus, and hypophosphatemia. No patients experienced grade 4 and above any treatment-related adverse events. Liver cancer is a common malignant tumor of digestive system worldwide.

Nofazinlimab is a humanized recombinant IgG4 monoclonal antibody targeting human programmed cell death protein 1 (PD-1) being developed in solid tumors. Nofazinlimab shows comparable high binding affinities to the PD-1 of humans, cynomolgus monkey, and mouse, and can block the interaction of PD-1 with its ligands PD-L1 and PD-L2.