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

Hepatocellular Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04194775
• Other study ID #: CS1003-305
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 13, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: July 2023
• Source: CStone Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 534
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Nofazinlimab (CS1003)+Lenvatinib
Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily
• Nofazinlimab (CS1003) Placebo+Lenvatinib
Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily

Locations

Country	Name	City	State
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 First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
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	Sichuan University - West China Hospital	Chengdu	Sichuan
China	Foshan First People's Hospital	Foshan	Guangdong
China	The 900th Hospital of Joint Logistic Support Force of PLA	Fuzhou	Fujian
China	Nanfang Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Hainan General Hospital - Hepatology	Haikou	Hainan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The First Affiliated Hospital Of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First People's Hospital of Huai'an	Huai'an	Jiangsu
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	Luoyang Central Hospital	Luoyang	Henan
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	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	Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University - Cancer Institute & Hospital - Oncology	Tianjin	Tianjin
China	hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital - Medical Oncology	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Yanbian University Hospital	Yanbian	Jilin
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Zhengzhou University - First Affiliated Hospital	Zhengzhou	Henan
Italy	PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology	Cremona
Italy	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	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Casa di Cura Dott. Pederzoli S.p.A (Ospedale Pederzoli)	Peschiera Del Garda	Verona
Poland	Centrum Onkologii im. prof. F. Lukaszczyka	Bydgoszcz
Poland	MED-POLONIA Sp.z o.o.	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa
Poland	Centrum Badan Klinicznych	Wroclaw	Dolnoslaskie
Spain	Complexo Hospitalario Universitario A Coruña	A Coruna	Galicia
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	Hospital Universitario Puerta De Hierro De Majadahonda	Majadahonda	Madrid
Spain	H.U.V.Arrixaca	Murcia
Spain	Complejo Hospitalario Universitario de Orense	Ourense	Galicia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario Virgen De La Macarena	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Spain	Hospital Unviersitario Miguel Servet	Zaragoza
Taiwan	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
United States	Mercy Medical Center	Baltimore	Maryland
United States	Southern California Research Center	Coronado	California
United States	Inland Empire Liver Foundation	Rialto	California
United States	Stony Brook University Cancer Clinical Trials	Stony Brook	New York
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
CStone Pharmaceuticals

Countries where clinical trial is conducted

United States,  China,  Italy,  Poland,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)		Expected to be 5.5 years after the first patient is enrollment.
Secondary	Objective response rate (ORR) assessed by blinded independent central review committee(BICR)		Expected to be 5.5 years after the first patient is enrollment.
Secondary	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.
Secondary	Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1		Expected to be 5.5 years after the first patient is enrollment.
Secondary	Objective response rate (ORR) evaluated by investigators based on RECIST v1.1		Expected to be 5.5 years after the first patient is enrollment.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Percentage of Participants with Adverse Events		Expected to be 5.5 years after the first patient is enrollment.
Secondary	Peak and trough serum concentrations of CS1003		Expected to be 5.5 years after the first patient is enrollment.
Secondary	Number and percentage of subjects who develop anti-CS1003 antibody (ADA)		Expected to be 5.5 years after the first patient is enrollment.
Secondary	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.