Locally Advanced or Metastatic and Unresectable HCCPhase 3NCT03764293

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

A Phase 3 study testing SHR-1210, Apatinib and Sorafenib in people with Locally Advanced or Metastatic and Unresectable HCC, run by Jiangsu HengRui Medicine Co., Ltd. at 121 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line therapy in patients with advanced HCC. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Locally Advanced or Metastatic and Unresectable HCC
What is being tested?: SHR-1210, Apatinib and Sorafenib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 543 participants
Where: 121 sitesin 13 countries
Study dates: 10 Jun 2019to 14 Jun 2023
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

121 sites in 13 countries.

Country

City, postcode or hospital

121 sites in 13 countries

China37 sites

Chinese Academy of Medical Sciences Cancer Hospital
Beijing, Beijing Municipality, 100020
Beijing cancer Hospital
Beijing, Beijing Municipality, 100089
Peking University International Hospital
Beijing, Beijing Municipality, 102206
Jilin Cancer Hospital
Changchun, Jilin, 130000
The First Hospital of Jilin University
Changchun, Jilin, 130000
Hunan Cancer Hospital
Changsha, Hunan, 410006
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Sichuan Cancer Hospital&Institute
Chengdu, Sichuan, 610054
The Second Hospital Affiliated To AMU
Chongqing, Chongqing Municipality, 400037
The First Hospital Affiliated To AMU
Chongqing, Chongqing Municipality, 400038
TheThird Affiliated Hospital ,Army Medical University
Chongqing, Chongqing Municipality, 400042
The Second Affiliated Hospital of ChongQing Medical University
Chongqing, Chongqing Municipality, 400060
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Sun Yat-sen Memorial Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510220
NanFang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515
Sir Run Run Shaw Hospital
Hangzhou, Zhejiang, 310016
ZheJiang Cancer Hospital
Hangzhou, Zhejiang, 310022
The First Affiliated Hospital, Zhejiang University
Hangzhou, Zhejiang
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000
Anhui Provincal Cancer Hospital
Hefei, Anhui, 230000
Anhui Provincal Hospital
Hefei, Anhui, 230000
The First Affiliated Hospital Of Anhui Medical University
Hefei, Anhui, 230009
The Second Affiliated Hospital Of Anhui Medical University
Hefei, Anhui, 230601
Shandong Cancer Hospital Affiliated to Shandong University
Jinan, Shandong, 250000
The 940th Hospital of the joint logistic support force of People's Liberation Army
Lanzhou, Gansu
The First Affiliated Hospital Of Nanchang University
Nanchang, Jiangxi, 330006
Eastern Theater General Hospital, Qinhuai District Medical Area
Nanjing, Jiangsu, 210002
The first affiliated hospital of guangxi medical university
Nanning, Guangxi, 530021
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200032
Shanghai Changhai Hospital
Shanghai, Shanghai Municipality, 200043
The Sixth People's Hospital of Shengyang
Shengyang, Liaoning, 110006
Liaoning Cancer Hospital
Shenyang, Liaoning, 110042
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050011
Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology
Wuhan, Hubei, 430022
Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology
Wuhan, Hubei, 430030

Other trials in China

Russia13 sites

SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
Arkhangelsk, 164045
SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
Chelyabinsk, 454087
Irkutsk Regional Oncology Dispensary
Irkutsk, 664035
SBIH " Clinical Oncological Dispensary # 1"
Krasnodar, 350040
RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee
Kursk, 305035
"VitaMed" LLC
Moscow, 121309
SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement
Moscow, 143423
CJSC Avicenna
Novosibirsk, 630099
BHI of Omsk region "Clinical Oncology Dispensary"
Omsk, 644013
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, 197022
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
Saint Petersburg, 197758
SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
Ufa, 450054

Other trials in Russia

United States8 sites

University of Maryland
Baltimore, Maryland, 21201
Beverly Hills Cancer Center
Beverly Hills, California, 90211
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
MD Anderson Cancer Center
Houston, Texas, 77030
University of California San Diego (UCSD)-Moores Cancer Center
La Jolla, California, 92037
Cornell University Weill Cornell Medical College
New York, New York, 10065
University of California - Irvine
Orange, California, 92868
Renovatio Clinical
The Woodlands, Texas, 77380

Other trials in United States

Italy8 sites

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
Bologna, 40138
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, 25123
Azienda Ospedaliero-Universitaria
Cagliari, 09124
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
Milan, 20122
A.S.L. Napoli 1 Centro Ospedale del Mare
Ponticelli, Napoli, 80147
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
Verona, 37134

Other trials in Italy

Poland8 sites

Centrum Medyczne Pratia Gdynia
Gdynia, 81338
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
Gliwice, 44101
Pratia MCM Krakow
Krakow, 30510
Przychodnia Med-Polonia Sp. z o.o.
Poznan, 60693
Wielkopolskie Centrum Onkologii
Poznan, 61866
Centrum Zdrowia MDM
Warsaw, 00635
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, 02034
NZOZ Centrum Badan Klinicznych
Wroclaw, 51162

Other trials in Poland

South Korea8 sites

Dong-A University Hospital
Busan, 602715
Seoul National University Bundang Hospital Gyeonggi-do
Seongnam-si, Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 02481
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, St. Vincent's Hospital
Suwon, Gyeonggi-do, 16247
Ajou University Hospital
Suwon, Gyeonggi-do, 16499

Other trials in South Korea

Taiwan8 sites

Changhua Christian Medical Foundation Changhua Christian Hospital
Changhua, 500006
Chang Gung Memorial Hospital, Chiayi
Chiayi City, 613
E-DA Cancer Hospital
Kaohsiung City, 82445
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 11217
Chang Gung Memorial Hospital, Linkou
Taoyuan, 333

Other trials in Taiwan

Ukraine8 sites

CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
Dnipro, 49102
Communal Non-profit Enterprise Regional Center of Oncology
Kharkiv, 61070
CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
Kharkiv, 61166
Medical Center of Limited Liability Company Medical Center Concilium Medical
Kyiv, 04050
Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council
Lutsk, 43018
Communal Institution Odesa Regional Clinical Hospital
Odesa, 65025
CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology
Sumy, 40022
Zaporizhzhya City Clinical Hospital #3
Zaporizhzhya, 69032

Other trials in Ukraine

Spain7 sites

Hospital Universitario Reina Sofia
Córdoba, Córdoba, 14004
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Clinico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario HM Madrid Sanchinarro
Madrid, 28050
Hospital Universitari i Politecnic La Fe
Valencia, 46026

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Turkey (Türkiye)6 sites

Baskent University Adana Application and Research Center
Adana, 01229
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
Ankara, 06105
Ankara City Hospital
Ankara, 06800
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
Istanbul, 34098
Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital
Istanbul, 34147
Inonu Uni. Med. Fac.
Malatya, 44280

Other trials in Turkey (Türkiye)

Belgium5 sites

Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, 1070
Cliniques Universitaires Saint-Luc
Brussels, 1200
UZA
Edegem, 2650
AZ Maria Middelares
Ghent, 9000
AZ Groeninge
Kortrijk, 8500

Other trials in Belgium

Hong Kong4 sites

Pamela Youde Nethersole Eastern Hospital
Hong Kong
The University of Hong Kong
Hong Kong
Tuen Mun Hospital
Hong Kong
The Chinese University of Hong Kong
Shatin

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Germany1 site

Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin
Berlin, 13353

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About this study

Official title: A 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

Conditions: Locally Advanced or Metastatic and Unresectable HCC
Being tested: SHR-1210, Apatinib, Sorafenib
Medical subject headings: Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SHR-1210Drug
Also called Camrelizumab
Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial
ApatinibDrug
Also called Rivoceranib
Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet
SorafenibDrug
Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet

Study groups in NCT03764293
Study group	Role	What they receive
SHR-1210	Experimental	SHR-1210+Apatinib Receives: Drug: SHR-1210; Drug: Apatinib
Control	Active comparator	Sorafenib Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Measured: Up to approximately 3 years
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.
Measured: Up to approximately 3 years

Secondary outcomes (3)

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.
Measured: Up to approximately 3 years
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.
Measured: Up to approximately 3 years
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.
Measured: Up to approximately 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jun 201914 Jun 2023

First posted5 Dec 2018
Study start10 Jun 2019
Primary completion8 Feb 2022
Study completion14 Jun 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Locally Advanced or Metastatic and Unresectable HCCStudies of the same condition, open and under way.
More trials run by Jiangsu HengRui Medicine Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 543 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03764293
Sponsor's protocol ID: SHR-1210-III-310
Status last verified: Feb 2023
First submitted: 28 Nov 2018
Last updated: 6 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Qin S, Gu S, Chan SL, Bai Y, Ren Z, Lin X, Chen Z, Jia W, Jin Y, Guo Y, Hu X, Meng Z, Liang J, Xiong J, Ren H, Yang F, Li W, Chen Y, Zeng Y, Xu L, Yuan X, Li D, Sultanbaev A, Pazgan-Simon M, Pisetska M, Melisi D, Ponomarenko D, Du J, Shi W, Cheng AL, Kaseb A, Vogel A; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study. Lancet Oncol. 2025 Dec;26(12):1598-1611. doi: 10.1016/S1470-2045(25)00543-1.
PubMed 41308676
Qin S, Chan SL, Gu S, Bai Y, Ren Z, Lin X, Chen Z, Jia W, Jin Y, Guo Y, Hu X, Meng Z, Liang J, Cheng Y, Xiong J, Ren H, Yang F, Li W, Chen Y, Zeng Y, Sultanbaev A, Pazgan-Simon M, Pisetska M, Melisi D, Ponomarenko D, Osypchuk Y, Sinielnikov I, Yang TS, Liang X, Chen C, Wang L, Cheng AL, Kaseb A, Vogel A; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023 Sep 30;402(10408):1133-1146. doi: 10.1016/S0140-6736(23)00961-3. Epub 2023 Jul 24.
PubMed 37499670