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 of 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
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
    • Beijing, Beijing, 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
    • Shanghai, Shanghai, China
      • Shanghai First People's Hospital
    • Shanghai, Shanghai, China, 201203
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China
      • Shanghai Cancer Hospital of Fudan University
    • Shanghai, Shanghai, China
      • Shanghai Eastern Hepatobiliary Surgery Hospital - Hepatology
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan University - West China Hospital
  • Tianjin
    • Tianjin, Tianjin, 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
  • Warszawa, Poland
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland
      • Centrum Badan Klinicznych
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland
      • MED-POLONIA Sp.z o.o.
• Spain
  • Avila, Spain
    • Hospital Ntra. Sra. de Sonsoles
  • 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 Maranon
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Murcia, Spain
    • H.U.V.Arrixaca
  • Sevilla, Spain
    • Hospital Universitario Virgen De La Macarena
  • Valencia, Spain
    • Consorcio Hospital General Universitario de Valencia
  • Zaragoza, Spain
    • Hospital Unviersitario Miguel Servet
  • Asturias
    • Oviedo, Asturias, Spain
      • Hospital Universitario Central de Asturias
  • Galicia
    • A Coruna, 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
• 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	Time Frame
Overall survival (OS)	Expected to be 5.5 years after the first patient is enrollment.

Secondary Outcome Measures

Outcome Measure	Time Frame
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.
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.
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.
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.
Percentage of Participants with Adverse Events	Expected to be 5.5 years after the first patient is enrollment.
Peak and trough serum concentrations of CS1003	Expected to be 5.5 years after the first patient is enrollment.
Number and percentage of subjects who develop anti-CS1003 antibody (ADA)	Expected to be 5.5 years after the first patient is enrollment.
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.

Collaborators and Investigators

• Sponsor: CStone Pharmaceuticals

Study record dates

Study Major Dates

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

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 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• 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