CStone announced the global multi-regional registration trial of anti-PD-1 antibody nofazinlimab in combination with lenvatinib as first-line treatment for patients with advanced hepatocellular carcinoma successfully reached the prespecified enrollment ta

SUZHOU,China,March 18,2022 --CStone Pharmaceuticals ("CStone",HKEX: 2616),a leading biopharmaceutical company focused on research,development,and commercialization of innovative immuno-oncology therapies and precision medicines,today 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.

"We are pleased that the CS1003-305 trial met the prespecified patient enrollment target ahead of schedule. It's our third large registrational trial which has recently achieved the prespecified enrollment target in high incidence gastrointestinal cancer,following the two ongoing studies of sugemalimab as first-line treatment of gastric cancer and esophageal squamous cell carcinoma," said Dr. Jason Yang,Chief Medical Officer of CStone. "Early phase clinical trial results[1] showed that nofazinlimab in combination with lenvatinib shows promising anti-tumor activity and a manageable safety profile in Chinese patients with unresectable HCC as 1L treatment. Nofazinlimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) in 2020. We look forward to bringing this promising treatment option to the patients with advanced HCC worldwide."

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.

About hepatocellular carcinoma (HCC)

Liver cancer is a common malignant tumor of digestive system worldwide. According to GLOBOCAN 2020 (Global Cancer Incidence,Mortality and Prevalence) data of the International Agency for Research on Cancer (IARC),a specialized agency of the World Health Organization,global new cases of liver cancer is more than 900,000,and death cases are more than 830,000 per year. The number of death cases is close to the number of new cases. Liver cancer is the second leading cause of cancer- related death and its incidence is increasing globally[2]. HCC is the most common form of liver cancer and accounts for ~90% of cases[3]. Systemic antitumor therapy plays an important role in the treatment of advanced HCC. Despite the expanding implementation of surgical and locoregional therapies worldwide,estimates suggest that ~50–60% of patients with HCC will ultimately be treated with systemic therapies[2]. A median survival for symptomatic advanced-stage HCC cases treated with systemic therapies is ~1–1.5 years[3]. Poor prognosis of HCC is attributed primarily to tumor presentation at an advanced stage when there is no effective treatment to achieve the long term survival of patients[4].

About nofazinlimab (CS1003)

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.

The U.S. FDA has granted nofazinlimab Orphan Drug Designation (ODD) in July 2020 for the treatment of patients with HCC.

CStone formed a strategic collaboration agreement with EQRx,under which EQRx licensed the exclusive rights to two immuno-oncology assets,sugemalimab andnofazinlimab,for development and commercialization outside of Greater China.CStone retains rights to nofazinlimab in Greater China,where it can continue to pursue development as a monotherapy or as part of its combination strategy for this drug.

About CStone

CStone (HKEX: 2616) is a biopharmaceutical company focused on research,and commercialization of innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015,CStone has assembled a world-class management team with extensive experience in innovative drug development,clinical research,and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently,CStone has received seven NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone's vision is to become globally recognized as a world-renowned biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

For more information about CStone,please visit www.cstonepharma.com.

Forward-looking statement

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Reference:

Shen L et al,ESMO Congress 2020,Abstract 987P,A Phase 1b study of the PD-1 antagonist CS1003 plus lenvatinib (LEN) in Chinese patients (pts) with the first-line (1L) unresectable hepatocellular carcinoma (uHCC).

Llovet JM et al,Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. Immunotherapies for hepatocellular carcinoma

Llovet JM et al,Nat Rev Dis Primers. 2021 Jan 21;7(1):6. Hepatocellular carcinoma.

Ahn JC et al,Hepatology. 2021 Jan;73(1):422-436. Detection of Circulating Tumor Cells and Their Implications as a Biomarker for Diagnosis,Prognostication,and Therapeutic Monitoring in Hepatocellular Carcinoma

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