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

NCT04194775 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CS1003-305
• Study Type: interventional
• Target: 534
• Locations: 6 countries
• Sites: 74

Brief Summary

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 of and lenvatinib is selected as the basic treatment for HCC.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Expected to be 5.5 years after the first patient is enrollment.

Secondary Outcomes (12)

• Objective response rate (ORR) assessed by blinded independent central review committee(BICR)

  Expected to be 5.5 years after the first patient is enrollment.

• Progression-free survival(PFS) assessed by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1

  Expected to be 5.5 years after the first patient is enrollment.

• Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1

  Expected to be 5.5 years after the first patient is enrollment.

• Objective response rate (ORR) evaluated by investigators based on RECIST v1.1

  Expected to be 5.5 years after the first patient is enrollment.

• Duration of response (DoR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1

  Expected to be 5.5 years after the first patient is enrollment.

Study Arms (2)

Nofazinlimab (CS1003)

EXPERIMENTAL

Drug: Nofazinlimab (CS1003)+Lenvatinib

Nofazinlimab (CS1003) placebo

PLACEBO COMPARATOR

Drug: Nofazinlimab (CS1003) Placebo+Lenvatinib

Interventions

Nofazinlimab (CS1003)+Lenvatinib DRUG

Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily

Nofazinlimab (CS1003)

Nofazinlimab (CS1003) Placebo+Lenvatinib DRUG

Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily

Nofazinlimab (CS1003) placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years).
• 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.
• With at least one measurable lesion can be assessed
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Life expectancy ≥ 3 months.
• Child-Pugh A
• No prior systemic treatment for advanced HCC
• Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study.
• 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.

You may not qualify if:

• Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC.
• A prior bleeding event due to esophageal within 6 months or other gastrointestinal bleeding events within 28 days prior to screening.
• Malabsorption syndrome or inability to take oral medication due to other causes.
• HBV and HCV co-infection.
• 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.
• Surgery or locoregional therapy for palliative purpose within 4 weeks prior to study treatment.
• History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease.
• Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• 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.
• History of bone marrow transplantation or organ transplantation.
• History of anaphylaxis or hypersensitivity to any ingredient of the investigational product.
• Any contraindication of lenvatinib.
• Known history of drugs abuse that would interfere with cooperation with the requirements of the trial.
• Pregnant or lactating female subjects.
• History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability.

Sponsors & Collaborators

• CStone Pharmaceuticals: lead

Study Sites (74)

Southern California Research Center

Coronado, California, 92118, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Stony Brook University Cancer Clinical Trials

Stony Brook, New York, 11794, United States

Location

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Location

The First Affiliated Hospital Of Anhui Medical University

Hefei, Anhui, China

Location

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Beijing You'an Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

The 900th Hospital of Joint Logistic Support Force of PLA

Fuzhou, Fujian, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Location

Foshan First People's Hospital

Foshan, Guangdong, China

Location

Nanfang Hospital

Guangzhou, Guangdong, China

Location

The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

Guangzhou, Guangdong, China

Location

Guangxi Medical University Affiliated Tumor Hospital

Nanning, Guangxi, China

Location

Hainan General Hospital - Hepatology

Haikou, Hainan, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Location

Luoyang Central Hospital

Luoyang, Henan, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Zhengzhou University - First Affiliated Hospital

Zhengzhou, Henan, China

Location

hubei Cancer Hospital

Wuhan, Hubei, China

Location

Tongji Hospital - Medical Oncology

Wuhan, Hubei, China

Location

Hunan Cancer Hospital - Radiology

Changsha, Hunan, China

Location

Hunan Provincial People's Hospital

Changsha, Hunan, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

The First People's Hospital of Huai'an

Huai'an, Jiangsu, China

Location

Nantong Tumor Hospital

Nantong, Jiangsu, China

Location

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

Yanbian University Hospital

Yanbian, Jilin, China

Location

Jinan Military Region General Hospital of the People's Liber

Jinan, Shandong, China

Location

Shangdong Provicial Qianfoshan Hospital

Jinan, Shandong, China

Location

Affiliated Hospital Of Jining Medical University

Jining, Shandong, China

Location

Linyi Cancer Hospital

Linyi, Shandong, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 201203, China

Location

Shanghai Cancer Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Shanghai Eastern Hepatobiliary Surgery Hospital - Hepatology

Shanghai, Shanghai Municipality, China

Location

Shanghai First People's Hospital

Shanghai, Shanghai Municipality, China

Location

Sichuan University - West China Hospital

Chengdu, Sichuan, China

Location

Tianjin Medical University - Cancer Institute & Hospital - Oncology

Tianjin, Tianjin Municipality, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

Azienda Unità Locale Socio Sanitaria n. 1 Dolomiti, Distretto di Feltre, Ospedale di Feltre

Feltre, Belluno, Italy

Location

Istituto Oncologico Veneto IOV IRCCS - Medical Oncology Unit 1

Padua, Veneto, Italy

Location

Casa di Cura Dott. Pederzoli S.p.A (Ospedale Pederzoli)

Peschiera del Garda, Verona, Italy

Location

PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology

Cremona, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

MED-POLONIA Sp.z o.o.

Poznan, Greater Poland Voivodeship, Poland

Location

Centrum Badan Klinicznych

Wroclaw, Lower Silesian Voivodeship, Poland

Location

Centrum Onkologii im. prof. F. Lukaszczyka

Bydgoszcz, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, Poland

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, Galicia, Spain

Location

Complejo Hospitalario Universitario de Orense

Ourense, Galicia, Spain

Location

Hospital Universitario Puerta De Hierro De Majadahonda

Majadahonda, Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Location

Hospital Ntra. Sra. de Sonsoles

Ávila, Spain

Location

Hospital Del Mar

Barcelona, Spain

Location

H.U. de Burgos

Burgos, Spain

Location

ICO-Hospital Universitari de Girona Dr. Josep Trueta

Girona, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

H.U.V.Arrixaca

Murcia, Spain

Location

Hospital Universitario Virgen De La Macarena

Seville, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, Spain

Location

Hospital Unviersitario Miguel Servet

Zaragoza, Spain

Location

China Medical University Hospital - Internal Medicine - Taichung

Taichung, Taiwan

Location

Taichung Veterans General Hospital - Gastroenterology

Taichung, Taiwan

Location

Chi Mei Hospital, Liouying - Department of Oncology

Tainan, Taiwan

Location

Chi Mei Medical Center - YongKang - Gastroenterology - Gastroenterology

Tainan, Taiwan

Location

National Cheng Kung University Hospital - Internal Medicine

Tainan, Taiwan

Location

Tri-Service General Hospital - Neihu Branch - Pulmonary

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

CS-1003

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 11, 2019
• Study Start: December 13, 2019
• Primary Completion: June 18, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: December 11, 2025

Record last verified: 2025-12

Locations

TW (6); IT (5); CN (40); US (5); PL (4); ES (14)