A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified January 2023 by Jiangsu HengRui Medicine Co., Ltd.
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
Information Provided by (Responsible Party)
Jiangsu HengRui Medicine Co., Ltd.
Clinicaltrials.gov Identifier
NCT03764293
Other Study ID Numbers:
SHR-1210-III-310
First Submitted
November 27, 2018
First Posted
December 4, 2018
Results First Posted
November 9, 2023
Last Update Posted
February 5, 2024
Last Verified
January 2023

ClinicalTrials.gov processed this data on February 2024. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Locally Advanced or Metastatic and Unresectable HCC
Drug: SHR-1210Drug: Sorafenib

Study Design

Study TypeInterventional
Actual Enrollment543 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Randomized, Open-Label, International, Multi-Center, Phase 3 Clinical Study of PD-1 Antibody SHR-1210 Plus Apatinib Mesylate Versus Sorafenib as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Previously Received Systemic Therapy
Study Start DateJune 9, 2019
Actual Primary Completion DateFebruary 7, 2022
Actual Study Completion DateJune 13, 2023

Groups and Cohorts

Group/CohortIntervention/Treatment
SHR-1210
SHR-1210+Apatinib
Drug: SHR-1210
Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
Control
Sorafenib
Drug: Sorafenib
Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet

Outcome Measures

Primary Outcome Measures
  1. Overall Survival (OS)
    OS was defined as the time from randomization to death from any cause.
  2. Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1
    PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) by tumor image evaluation or death from any cause whichever occurs first as determined by BIRC according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions and the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm), or a measurable increase in a non-target lesion, or the appearance of new lesions.
Secondary Outcome Measures
  1. Objective Response Rate (ORR)
    ORR defined as the percentage of subjects with complete response (CR) or partial response (PR) evaluated by the BIRC or investigator based on RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Overall Response (OR)=CR+PR.
  2. Disease Control Rate (DCR)
    DCR defined as the percentage of subjects with complete response, partial response or stable disease (SD) ≥ 8 weeks evaluated by the BIRC or investigator based on RECIST v1.1. Complete response (CR) was defined as Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  3. Duration of Response (DOR)
    DOR defined as time from the date of first record of objective response (CR or PR) to the first occurrence of radiological progression or death, whichever comes first, evaluated by the BIRC or investigator based on RECIST v1.1. Complete response (CR) was defined as Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Histopathologically or cytologically confirmed advanced HCC
No previous systematic treatment for HCC
Have at least one measurable lesion (in accordance with RECIST v1.1)
BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy
ECOG-PS score 0 or 1
Child-Pugh Class: Grade A
Life Expectancy of at least 12 weeks
Subjects with HBV infection: HBV DNA\<500 IU/ml or \< 2500 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study
Subjects with HCV-RNA(+) must receive antiviral therapy
Adequate organ function
Exclusion Criteria
Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; other active malignant tumor except HCC within 5 years or simultaneously
Moderate-to-severe ascites with clinical symptoms
History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage
Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment
Known genetic or acquired hemorrhage or thrombotic tendency
Thrombosis or thromboembolic event within 6 months prior to the start of study treatment
Cardiac clinical symptom or disease that is not well controlled
Hypertension that can not be well controlled through antihypertensive drugs
Factors to affect oral administration
History of hepatic encephalopathy
Previous or current presence of metastasis to central nervous system
HIV infection
Combined hepatitis B and hepatitis C co-infection
Be ready for or previously received organ or allogenic bone marrow transplantation
Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
Active known, or suspected autoimmune disease
Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first administration of study treatment
Use of potent CYP3A4 inducers or inhibitors within 2 weeks prior to the signature of ICF
Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug
Severe infection within 4 weeks prior to the start of study treatment
Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it must be completed at least 2 weeks prior to the start of study treatment
Treatment of other investigational product(s) within 28 days prior to the start of study treatment

Contacts and Locations

Sponsors and CollaboratorsJiangsu HengRui Medicine Co., Ltd.
Locations
Beverly Hills Cancer Center | Beverly Hills California, United States, 90211University of California San Diego (UCSD)-Moores Cancer Center | La Jolla California, United States, 92037University of California - Irvine | Orange California, United States, 92868University of Maryland | Baltimore Maryland, United States, 21201Cornell University Weill Cornell Medical College | New York New York, United States, 10065The Center for Cancer and Blood Disorders | Fort Worth Texas, United States, 76104MD Anderson Cancer Center | Houston Texas, United States, 77030Renovatio Clinical | The Woodlands Texas, United States, 77380Cliniques Universitaires de Bruxelles Hopital Erasme | Brussels , Belgium, 1070Cliniques Universitaires Saint-Luc | Brussels , Belgium, 1200UZA | Edegem , Belgium, 2650AZ Maria Middelares | Ghent , Belgium, 9000AZ Groeninge | Kortrijk , Belgium, 8500Anhui Provincal Cancer Hospital | Hefei Anhui, China, 230000Anhui Provincal Hospital | Hefei Anhui, China, 230000The First Affiliated Hospital Of Anhui Medical University | Hefei Anhui, China, 230009The Second Affiliated Hospital Of Anhui Medical University | Hefei Anhui, China, 230601Chinese Academy of Medical Sciences Cancer Hospital | Beijing Beijing Municipality, China, 100020Beijing cancer Hospital | Beijing Beijing Municipality, China, 100089Peking University International Hospital | Beijing Beijing Municipality, China, 102206The Second Hospital Affiliated To AMU | Chongqing Chongqing Municipality, China, 400037The First Hospital Affiliated To AMU | Chongqing Chongqing Municipality, China, 400038TheThird Affiliated Hospital ,Army Medical University | Chongqing Chongqing Municipality, China, 400042The Second Affiliated Hospital of ChongQing Medical University | Chongqing Chongqing Municipality, China, 400060Fujian Medical University Union Hospital | Fuzhou Fujian, China, 350001The 940th Hospital of the joint logistic support force of People's Liberation Army | Lanzhou Gansu, China, Sun Yat-sen University Cancer Center | Guangzhou Guangdong, China, 510060Sun Yat-sen Memorial Hospital, Sun Yat-Sen University | Guangzhou Guangdong, China, 510220NanFang Hospital of Southern Medical University | Guangzhou Guangdong, China, 510515The first affiliated hospital of guangxi medical university | Nanning Guangxi, China, 530021The Fourth Hospital of Hebei Medical University | Shijiazhuang Hebei, China, 050011Harbin Medical University Cancer Hospital | Harbin Heilongjiang, China, 150000Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology | Wuhan Hubei, China, 430022Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology | Wuhan Hubei, China, 430030Hunan Cancer Hospital | Changsha Hunan, China, 410006Eastern Theater General Hospital, Qinhuai District Medical Area | Nanjing Jiangsu, China, 210002The First Affiliated Hospital Of Nanchang University | Nanchang Jiangxi, China, 330006Jilin Cancer Hospital | Changchun Jilin, China, 130000The First Hospital of Jilin University | Changchun Jilin, China, 130000The Sixth People's Hospital of Shengyang | Shengyang Liaoning, China, 110006Liaoning Cancer Hospital | Shenyang Liaoning, China, 110042Shandong Cancer Hospital Affiliated to Shandong University | Jinan Shandong, China, 250000Fudan University Shanghai Cancer Center | Shanghai Shanghai Municipality, China, 200032Zhongshan Hospital, Fudan University | Shanghai Shanghai Municipality, China, 200032Shanghai Changhai Hospital | Shanghai Shanghai Municipality, China, 200043West China Hospital of Sichuan University | Chengdu Sichuan, China, 610041Sichuan Cancer Hospital&Institute | Chengdu Sichuan, China, 610054Sir Run Run Shaw Hospital | Hangzhou Zhejiang, China, 310016ZheJiang Cancer Hospital | Hangzhou Zhejiang, China, 310022The First Affiliated Hospital, Zhejiang University | Hangzhou Zhejiang, China, Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin | Berlin , Germany, 13353Pamela Youde Nethersole Eastern Hospital | Hong Kong , Hong Kong, The University of Hong Kong | Hong Kong , Hong Kong, Tuen Mun Hospital | Hong Kong , Hong Kong, The Chinese University of Hong Kong | Shatin , Hong Kong, A.S.L. Napoli 1 Centro Ospedale del Mare | Ponticelli Napoli, Italy, 80147Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS | Bologna , Italy, 40138Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) | Brescia , Italy, 25123Azienda Ospedaliero-Universitaria | Cagliari , Italy, 09124Azienda Ospedaliera Universitaria Careggi | Florence , Italy, 50134Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico | Milan , Italy, 20122Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Roma , Italy, 00168Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) | Verona , Italy, 37134Centrum Medyczne Pratia Gdynia | Gdynia , Poland, 81338Centrum Onkologii-Instytut im.M.Sklodowskiej Curie | Gliwice , Poland, 44101Pratia MCM Krakow | Krakow , Poland, 30510Przychodnia Med-Polonia Sp. z o.o. | Poznan , Poland, 60693Wielkopolskie Centrum Onkologii | Poznan , Poland, 61866Centrum Zdrowia MDM | Warsaw , Poland, 00635Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy | Warsaw , Poland, 02034NZOZ Centrum Badan Klinicznych | Wroclaw , Poland, 51162SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" | Arkhangelsk , Russia, 164045SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine | Chelyabinsk , Russia, 454087Irkutsk Regional Oncology Dispensary | Irkutsk , Russia, 664035SBIH " Clinical Oncological Dispensary # 1" | Krasnodar , Russia, 350040RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee | Kursk , Russia, 305035"VitaMed" LLC | Moscow , Russia, 121309SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement | Moscow , Russia, 143423CJSC Avicenna | Novosibirsk , Russia, 630099BHI of Omsk region "Clinical Oncology Dispensary" | Omsk , Russia, 644013Pavlov First Saint Petersburg State Medical University | Saint Petersburg , Russia, 197022SPb SBIH "City Clinical Oncological Dispensary" | Saint Petersburg , Russia, 197022FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov" | Saint Petersburg , Russia, 197758SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan | Ufa , Russia, 450054Seoul National University Bundang Hospital Gyeonggi-do | Seongnam-si Gyeonggi-do, South Korea, 13620The Catholic University of Korea, St. Vincent's Hospital | Suwon Gyeonggi-do, South Korea, 16247Ajou University Hospital | Suwon Gyeonggi-do, South Korea, 16499Dong-A University Hospital | Busan , South Korea, 602715Korea University Anam Hospital | Seoul , South Korea, 02481Severance Hospital, Yonsei University Health System | Seoul , South Korea, 03722Asan Medical Center | Seoul , South Korea, 05505Samsung Medical Center | Seoul , South Korea, 06351Hospital Universitario Reina Sofia | Córdoba Córdoba, Spain, 14004Hospital Universitario Ramon y Cajal | Madrid , Spain, 28034Hospital Universitario Clinico San Carlos | Madrid , Spain, 28040Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitario La Paz | Madrid , Spain, 28046Hospital Universitario HM Madrid Sanchinarro | Madrid , Spain, 28050Hospital Universitari i Politecnic La Fe | Valencia , Spain, 46026Changhua Christian Medical Foundation Changhua Christian Hospital | Changhua , Taiwan, 500006Chang Gung Memorial Hospital, Chiayi | Chiayi City , Taiwan, 613E-DA Cancer Hospital | Kaohsiung City , Taiwan, 82445Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City , Taiwan, 833National Cheng Kung University Hospital | Tainan , Taiwan, 704National Taiwan University Hospital | Taipei , Taiwan, 100Taipei Veterans General Hospital | Taipei , Taiwan, 11217Chang Gung Memorial Hospital, Linkou | Taoyuan , Taiwan, 333Baskent University Adana Application and Research Center | Adana , Turkey (Türkiye), 01229Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital | Ankara , Turkey (Türkiye), 06105Ankara City Hospital | Ankara , Turkey (Türkiye), 06800Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty | Istanbul , Turkey (Türkiye), 34098Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital | Istanbul , Turkey (Türkiye), 34147Inonu Uni. Med. Fac. | Malatya , Turkey (Türkiye), 44280CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU | Dnipro , Ukraine, 49102Communal Non-profit Enterprise Regional Center of Oncology | Kharkiv , Ukraine, 61070CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection | Kharkiv , Ukraine, 61166Medical Center of Limited Liability Company Medical Center Concilium Medical | Kyiv , Ukraine, 04050Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council | Lutsk , Ukraine, 43018Communal Institution Odesa Regional Clinical Hospital | Odesa , Ukraine, 65025CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology | Sumy , Ukraine, 40022Zaporizhzhya City Clinical Hospital #3 | Zaporizhzhia , Ukraine, 69032
Investigators
Principal Investigator: Shukui Qin, MD, Eastern Theater General Hospital,QinHuai District Medical Area
Study Documents (Full Text)
Documents provided by Jiangsu HengRui Medicine Co., Ltd.: Study Protocol  September 20, 2022Documents provided by Jiangsu HengRui Medicine Co., Ltd.: Statistical Analysis Plan  April 18, 2022