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)

ClinicalTrials.gov processed this data on July 17, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING (See Contacts and Locations)
Verified July 2024 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 10, 2019
First Posted: December 11, 2019
Last Update Posted: July 18, 2024
Last Verified: July 2024
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Hepatocellular Carcinoma
  • Drug: Nofazinlimab (CS1003)+Lenvatinib
  • Drug: 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 13, 2019
Anticipated Primary Completion DateJune 30, 2025
Anticipated Study Completion DateJune 30, 2025

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

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival (OS) [Expected to be 5.5 years after the first patient is enrollment.]

    Secondary Outcome Measures

    1. Objective response rate (ORR) assessed by blinded independent central review committee(BICR) [Expected to be 5.5 years after the first patient is enrollment.]
    2. 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.]
    3. Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1 [Expected to be 5.5 years after the first patient is enrollment.]
    4. Objective response rate (ORR) evaluated by investigators based on RECIST v1.1 [Expected to be 5.5 years after the first patient is enrollment.]
    5. 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.]
    6. Duration of response (DoR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 [Expected to be 5.5 years after the first patient is enrollment.]
    7. Disease control rate (DCR) 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.]
    8. Disease control rate (DCR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 [Expected to be 5.5 years after the first patient is enrollment.]
    9. Percentage of Participants with Adverse Events [Expected to be 5.5 years after the first patient is enrollment.]
    10. Peak and trough serum concentrations of CS1003 [Expected to be 5.5 years after the first patient is enrollment.]
    11. Number and percentage of subjects who develop anti-CS1003 antibody (ADA) [Expected to be 5.5 years after the first patient is enrollment.]
    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 [Expected to be 5.5 years after the first patient is enrollment.]

    Eligibility Criteria

    Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
    Sexes Eligible for Study All
    Accepts Healthy Volunteers No
    Inclusion Criteria
    • ge ≥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.
    Exclusion Criteria
    • ibrolamellar-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.
    • QTc interval > 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG);
    • Any condition that would in the investigator's judgment, prevent the subject from participating in this study.

    Contacts and Locations

    Sponsors and Collaborators CStone Pharmaceuticals
    Locations
    • Southern California Research Center | Coronado, California, United States, 92118
    • Inland Empire Liver Foundation | Rialto, California, United States, 92377
    • Mercy Medical Center | Baltimore, Maryland, United States, 21202
    • UMass Memorial Medical Center | Worcester, Massachusetts, United States, 01655
    • Stony Brook University Cancer Clinical Trials | Stony Brook, New York, United States, 11794
    • The 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, China,
    • Beijing You'an Hospital, Capital Medical University | Beijing, Beijing, China,
    • Peking Union Medical College Hospital | Beijing, Beijing, 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, China, 201203
    • Shanghai Cancer Hospital of Fudan University | Shanghai, Shanghai, China,
    • Shanghai Eastern Hepatobiliary Surgery Hospital - Hepatology | Shanghai, Shanghai, China,
    • Shanghai First People's Hospital | Shanghai, Shanghai, China,
    • Sichuan University - West China Hospital | Chengdu, Sichuan, China,
    • Tianjin Medical University - Cancer Institute & Hospital - Oncology | Tianjin, Tianjin, 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,
    • Centrum Badan Klinicznych | Wroclaw, Dolnoslaskie, Poland,
    • MED-POLONIA Sp.z o.o. | Poznan, Wielkopolskie, Poland,
    • Centrum Onkologii im. prof. F. Lukaszczyka | Bydgoszcz, Poland,
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy | Warszawa, Poland,
    • Hospital Universitario Central de Asturias | Oviedo, Asturias, Spain,
    • Complexo Hospitalario Universitario A Coruña | A Coruna, Galicia, Spain,
    • Complejo Hospitalario Universitario de Orense | Ourense, Galicia, Spain,
    • Hospital Universitario Puerta De Hierro De Majadahonda | Majadahonda, Madrid, Spain,
    • Hospital Ntra. Sra. de Sonsoles | Avila, 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 | Sevilla, 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,

    More Information

    Additional Relevant MeSH Terms

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