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

A 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)

This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product and lenvatinib is selected as the basic treatment for HCC.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Nofazinlimab (CS1003)+Lenvatinib; Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 534
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time interval between the date of randomization to the date of death from any cause.	From enrollment to end of follow-up, a median of 42.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Committee(BICR)	ORR assessed by BICR was defined as the proportion of participants who achieve objective response (complete response [CR] or partial response [PR]) assessed by BICR based on RECIST v1.1.	From enrollment to end of follow-up, a median of 42.5 months
Progression-free Survival(PFS) Assessed by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1	PFS assessed by BICR was defined as the time from the date of randomization to disease progression assessed by BICR or death, whichever occurs first.	From enrollment to end of follow-up, a median of 42.5 months
Progression-free Survival(PFS) Evaluated by Investigator Based on RECIST v1.1		From enrollment to end of follow-up, a median of 42.5 months
Objective Response Rate (ORR) Evaluated by Investigators Based on RECIST v1.1		From enrollment to end of follow-up, a median of 42.5 months
Duration of Response (DoR) Evaluated by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1		From enrollment to end of follow-up, a median of 42.5 months
Duration of Response (DoR) Evaluated by Investigators Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1		From enrollment to end of follow-up, a median of 42.5 months
Disease Control Rate (DCR) Evaluated by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1		From enrollment to end of follow-up, a median of 42.5 months
Disease Control Rate (DCR) Evaluated by Investigators Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1		From enrollment to end of follow-up, a median of 42.5 months
Percentage of Participants With Adverse Events		From enrollment to end of follow-up, a median of 42.5 months
Peak and Trough Serum Concentrations of CS1003		Peak: assessed post-dose (within 30 minutes after the end of infusion) on Cycle 4 Day 1; Trough: assessed pre-dose (within 60 minutes prior to infusion) on Cycle 4 Day 1 (cycle length = 21 days).
Number and Percentage of Subjects Who Develop Anti-CS1003 Antibody (ADA)		From enrollment to end of follow-up, a median of 42.5 months
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		From enrollment to end of follow-up, a median of 42.5 months

Collaborators and Investigators

• Sponsor: CStone Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2019
• Primary Completion (Actual): June 18, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: December 10, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): July 30, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; CS-1003
• Other Study ID Numbers: CS1003-305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No