A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified November 2025 by CStone Pharmaceuticals
Sponsor
CStone Pharmaceuticals
Information Provided by (Responsible Party)
CStone Pharmaceuticals
Clinicaltrials.gov Identifier
NCT04194775
Other Study ID Numbers:
CS1003-305
First Submitted
December 9, 2019
First Posted
December 10, 2019
Last Update Posted
December 10, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Hepatocellular Carcinoma
Drug: Nofazinlimab (CS1003)+LenvatinibDrug: Nofazinlimab (CS1003) Placebo+Lenvatinib

Study Design

Study TypeInterventional
Actual Enrollment534 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC)
Study Start DateDecember 12, 2019
Actual Primary Completion DateJune 17, 2025
Actual Study Completion Date4mos 3w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Nofazinlimab (CS1003)
Drug: Nofazinlimab (CS1003)+Lenvatinib
Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily
Nofazinlimab (CS1003) placebo
Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib
Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily

Outcome Measures

Primary Outcome Measures
  1. Overall survival (OS)
Secondary Outcome Measures
  1. Objective response rate (ORR) assessed by blinded independent central review committee(BICR)
  2. Progression-free survival(PFS) assessed by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
  3. Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1
  4. Objective response rate (ORR) evaluated by investigators based on RECIST v1.1
  5. Duration of response (DoR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
  6. Duration of response (DoR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
  7. Disease control rate (DCR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
  8. Disease control rate (DCR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
  9. Percentage of Participants with Adverse Events
  10. Peak and trough serum concentrations of CS1003
  11. Number and percentage of subjects who develop anti-CS1003 antibody (ADA)
  12. Time to deterioration (TTD), defined as the time from randomization to the first deterioration of European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) scale

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Inclusion criteria 1. Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years). 2. Subjects with unresectable advanced HCC, that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer \[BCLC\] staging system, and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria. Patients without cirrhosis require histological confirmation of diagnosis. 3. With at least one measurable lesion can be assessed 4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. 5. Life expectancy ≥ 3 months. 6. Child-Pugh A 7. No prior systemic treatment for advanced HCC 8. Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study. 9. Subjects have adequate organ and marrow function. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use an contraceptive method(s) from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment.
Exclusion Criteria
Inclusion criteria 1. Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years). 2. Subjects with unresectable advanced HCC, that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer \[BCLC\] staging system, and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria. Patients without cirrhosis require histological confirmation of diagnosis. 3. With at least one measurable lesion can be assessed 4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. 5. Life expectancy ≥ 3 months. 6. Child-Pugh A 7. No prior systemic treatment for advanced HCC 8. Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study. 9. Subjects have adequate organ and marrow function. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use an contraceptive method(s) from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment. Exclusion criteria 10. Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC. 11. A prior bleeding event due to esophageal within 6 months or other gastrointestinal bleeding events within 28 days prior to screening. 12. Malabsorption syndrome or inability to take oral medication due to other causes. 13. HBV and HCV co-infection. 14. Investigator evaluates to increase the drug related risk caused by enrolling subjects in trial and taking study drug, or any serious or uncontrolled systematic disease that confound the drug absorption or the study outcome, e,g diabetes mellitus, hypertension, rheumatoid arthritis, major cardiovascular disease and so on. 15. Surgery or locoregional therapy for palliative purpose within 4 weeks prior to study treatment. 16. History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease. 17. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). 18. Current or prior use of systemic corticosteroid (\> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study treatment. 19. History of bone marrow transplantation or organ transplantation. 20. History of anaphylaxis or hypersensitivity to any ingredient of the investigational product. 21. Any contraindication of lenvatinib. 22. Known history of drugs abuse that would interfere with cooperation with the requirements of the trial. 23. Pregnant or lactating female subjects. 24. History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability. 25. QTc interval \> 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG); 26. Any condition that would in the investigator's judgment, prevent the subject from participating in this study.

Contacts and Locations

Sponsors and CollaboratorsCStone Pharmaceuticals
Locations
Southern California Research Center | Coronado California, United States, 92118Inland Empire Liver Foundation | Rialto California, United States, 92377Mercy Medical Center | Baltimore Maryland, United States, 21202UMass Memorial Medical Center | Worcester Massachusetts, United States, 01655Stony Brook University Cancer Clinical Trials | Stony Brook New York, United States, 11794The First Affiliated Hospital of Bengbu Medical College | Bengbu Anhui, China, The First Affiliated Hospital Of Anhui Medical University | Hefei Anhui, China, The Second Affiliated Hospital of Anhui Medical University | Hefei Anhui, China, Beijing Cancer Hospital | Beijing Beijing Municipality, China, Beijing You'an Hospital, Capital Medical University | Beijing Beijing Municipality, China, Peking Union Medical College Hospital | Beijing Beijing Municipality, China, The 900th Hospital of Joint Logistic Support Force of PLA | Fuzhou Fujian, China, The First Affiliated Hospital of Xiamen University | Xiamen Fujian, China, Foshan First People's Hospital | Foshan Guangdong, China, Nanfang Hospital | Guangzhou Guangdong, China, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine | Guangzhou Guangdong, China, Guangxi Medical University Affiliated Tumor Hospital | Nanning Guangxi, China, Hainan General Hospital - Hepatology | Haikou Hainan, China, Harbin Medical University Cancer Hospital | Harbin Heilongjiang, China, Luoyang Central Hospital | Luoyang Henan, China, Henan Cancer Hospital | Zhengzhou Henan, China, Zhengzhou University - First Affiliated Hospital | Zhengzhou Henan, China, hubei Cancer Hospital | Wuhan Hubei, China, Tongji Hospital - Medical Oncology | Wuhan Hubei, China, Hunan Cancer Hospital - Radiology | Changsha Hunan, China, Hunan Provincial People's Hospital | Changsha Hunan, China, The Third Xiangya Hospital of Central South University | Changsha Hunan, China, The First People's Hospital of Huai'an | Huai'an Jiangsu, China, Nantong Tumor Hospital | Nantong Jiangsu, China, The Second Affiliated Hospital of Soochow University | Suzhou Jiangsu, China, Xuzhou Central Hospital | Xuzhou Jiangsu, China, The Second Affiliated Hospital of Nanchang University | Nanchang Jiangxi, China, Yanbian University Hospital | Yanbian Jilin, China, Jinan Military Region General Hospital of the People's Liber | Jinan Shandong, China, Shangdong Provicial Qianfoshan Hospital | Jinan Shandong, China, Affiliated Hospital Of Jining Medical University | Jining Shandong, China, Linyi Cancer Hospital | Linyi Shandong, China, The Affiliated Hospital of Qingdao University | Qingdao Shandong, China, Zhongshan Hospital, Fudan University | Shanghai Shanghai Municipality, China, 201203Shanghai Cancer Hospital of Fudan University | Shanghai Shanghai Municipality, China, Shanghai Eastern Hepatobiliary Surgery Hospital - Hepatology | Shanghai Shanghai Municipality, China, Shanghai First People's Hospital | Shanghai Shanghai Municipality, China, Sichuan University - West China Hospital | Chengdu Sichuan, China, Tianjin Medical University - Cancer Institute & Hospital - Oncology | Tianjin Tianjin Municipality, China, Zhejiang Cancer Hospital | Hangzhou Zhejiang, China, Azienda Unità Locale Socio Sanitaria n. 1 Dolomiti, Distretto di Feltre, Ospedale di Feltre | Feltre Belluno, Italy, Istituto Oncologico Veneto IOV IRCCS - Medical Oncology Unit 1 | Padova Veneto, Italy, Casa di Cura Dott. Pederzoli S.p.A (Ospedale Pederzoli) | Peschiera del Garda Verona, Italy, PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology | Cremona , Italy, Fondazione IRCCS Policlinico San Matteo | Pavia , Italy, MED-POLONIA Sp.z o.o. | Poznan Greater Poland Voivodeship, Poland, Centrum Badan Klinicznych | Wroclaw Lower Silesian Voivodeship, Poland, Centrum Onkologii im. prof. F. Lukaszczyka | Bydgoszcz , Poland, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy | Warsaw , Poland, Complexo Hospitalario Universitario A Coruña | A Coruña Galicia, Spain, Complejo Hospitalario Universitario de Orense | Ourense Galicia, Spain, Hospital Universitario Puerta De Hierro De Majadahonda | Majadahonda Madrid, Spain, Hospital Universitario Central de Asturias | Oviedo Principality of Asturias, Spain, Hospital Ntra. Sra. de Sonsoles | Ávila , Spain, Hospital Del Mar | Barcelona , Spain, H.U. de Burgos | Burgos , Spain, ICO-Hospital Universitari de Girona Dr. Josep Trueta | Girona , Spain, Hospital General Universitario Gregorio Marañón | Madrid , Spain, Hospital Universitario La Paz | Madrid , Spain, H.U.V.Arrixaca | Murcia , Spain, Hospital Universitario Virgen De La Macarena | Seville , Spain, Consorcio Hospital General Universitario de Valencia | Valencia , Spain, Hospital Unviersitario Miguel Servet | Zaragoza , Spain, China Medical University Hospital - Internal Medicine - Taichung | Taichung , Taiwan, Taichung Veterans General Hospital - Gastroenterology | Taichung , Taiwan, Chi Mei Hospital, Liouying - Department of Oncology | Tainan , Taiwan, Chi Mei Medical Center - YongKang - Gastroenterology - Gastroenterology | Tainan , Taiwan, National Cheng Kung University Hospital - Internal Medicine | Tainan , Taiwan, Tri-Service General Hospital - Neihu Branch - Pulmonary | Taipei , Taiwan,