Clinical trial NCT04194775: A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Lead sponsor: CStone Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-12-11
Enrollment: 534
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
Secondary outcomes:
measure: Objective response rate (ORR) assessed by blinded independent central review committee(BICR)
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Progression-free survival(PFS) assessed by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Progression-free survival(PFS) evaluated by investigator based on RECIST v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Objective response rate (ORR) evaluated by investigators based on RECIST v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Duration of response (DoR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Duration of response (DoR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Disease control rate (DCR) evaluated by blinded independent central review committee(BICR) based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Disease control rate (DCR) evaluated by investigators based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Percentage of Participants with Adverse Events
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Peak and trough serum concentrations of CS1003
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: Number and percentage of subjects who develop anti-CS1003 antibody (ADA)
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
measure: 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
timeFrame: Expected to be 5.5 years after the first patient is enrollment.
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Clinical Trials
state: New York
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital Of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing You'an Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: The 900th Hospital of Joint Logistic Support Force of PLA
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital - Hepatology
state: Hainan
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou University - First Affiliated Hospital
state: Henan
city: Wuhan
country: China
facility: hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital - Medical Oncology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital - Radiology
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Huai'an
country: China
facility: The First People's Hospital of Huai'an
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Yanbian
country: China
facility: Yanbian University Hospital
state: Jilin
city: Jinan
country: China
facility: Jinan Military Region General Hospital of the People's Liber
state: Shandong
city: Jinan
country: China
facility: Shangdong Provicial Qianfoshan Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital Of Jining Medical University
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Cancer Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Eastern Hepatobiliary Surgery Hospital - Hepatology
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First People's Hospital
state: Shanghai
city: Chengdu
country: China
facility: Sichuan University - West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University - Cancer Institute & Hospital - Oncology
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Feltre
country: Italy
facility: Azienda Unità Locale Socio Sanitaria n. 1 Dolomiti, Distretto di Feltre, Ospedale di Feltre
state: Belluno
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IOV IRCCS - Medical Oncology Unit 1
state: Veneto
city: Peschiera Del Garda
country: Italy
facility: Casa di Cura Dott. Pederzoli S.p.A (Ospedale Pederzoli)
state: Verona
city: Cremona
country: Italy
facility: PO di Cremona, ASST di Cremona - Oncologia - Cremona - Radiology
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Wroclaw
country: Poland
facility: Centrum Badan Klinicznych
state: Dolnoslaskie
city: Poznan
country: Poland
facility: MED-POLONIA Sp.z o.o.
state: Wielkopolskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. F. Lukaszczyka
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: A Coruna
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
state: Galicia
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Orense
state: Galicia
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta De Hierro De Majadahonda
state: Madrid
city: Avila
country: Spain
facility: Hospital Ntra. Sra. de Sonsoles
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Burgos
country: Spain
facility: H.U. de Burgos
city: Girona
country: Spain
facility: ICO-Hospital Universitari de Girona Dr. Josep Trueta
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: H.U.V.Arrixaca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Unviersitario Miguel Servet
city: Taichung
country: Taiwan
facility: China Medical University Hospital - Internal Medicine - Taichung
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital - Gastroenterology
city: Tainan
country: Taiwan
facility: Chi Mei Hospital, Liouying - Department of Oncology
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center - YongKang - Gastroenterology - Gastroenterology
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital - Internal Medicine
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital - Neihu Branch - Pulmonary
Study officials:
References: