A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC Clinical Trial Results and Information

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

ClinicalTrials.gov processed this data on February 5, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED - HAS RESULTS
(See Contacts and Locations)
Verified February 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 28, 2018
First Posted: December 5, 2018
Results First Posted: February 6, 2024
Last Update Posted: February 6, 2024
Last Verified: February 2023
History of Changes

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Study Description

Not Provided

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

Study Design

Study Type	Interventional
Actual Enrollment	543 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
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
Study Start Date	June 10, 2019
Actual Primary Completion Date	February 8, 2022
Actual Study Completion Date	June 14, 2023

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
SHR-1210 SHR-1210+Apatinib	Drug: SHR-1210 Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial Drug: Apatinib
Control Sorafenib	Drug: Sorafenib

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Up to approximately 3 years]
OS was defined as the time from randomization to death from any cause.
Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1 [Up to approximately 3 years]
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

Objective Response Rate (ORR) [Up to approximately 3 years]
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.
Disease Control Rate (DCR) [Up to approximately 3 years]
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.
Duration of Response (DOR) [Up to approximately 3 years]
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	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
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 Collaborators	Jiangsu HengRui Medicine Co., Ltd.
Locations	Beverly Hills Cancer Center \| Beverly Hills, California, United States, 90211 University of California San Diego (UCSD)-Moores Cancer Center \| La Jolla, California, United States, 92037 University of California - Irvine \| Orange, California, United States, 92868 University of Maryland \| Baltimore, Maryland, United States, 21201 Cornell University Weill Cornell Medical College \| New York, New York, United States, 10065 The Center for Cancer and Blood Disorders \| Fort Worth, Texas, United States, 76104 MD Anderson Cancer Center \| Houston, Texas, United States, 77030 Renovatio Clinical \| The Woodlands, Texas, United States, 77380 Cliniques Universitaires de Bruxelles Hopital Erasme \| Bruxelles, Belgium, 1070 Cliniques Universitaires Saint-Luc \| Bruxelles, Belgium, 1200 UZA \| Edegem, Belgium, 2650 AZ Maria Middelares \| Gent, Belgium, 9000 AZ Groeninge \| Kortrijk, Belgium, 8500 Anhui Provincal Cancer Hospital \| Hefei, Anhui, China, 230000 Anhui Provincal Hospital \| Hefei, Anhui, China, 230000 The First Affiliated Hospital Of Anhui Medical University \| Hefei, Anhui, China, 230009 The Second Affiliated Hospital Of Anhui Medical University \| Hefei, Anhui, China, 230601 Chinese Academy of Medical Sciences Cancer Hospital \| Beijing, Beijing, China, 100020 Beijing cancer Hospital \| Beijing, Beijing, China, 100089 Peking University International Hospital \| Beijing, Beijing, China, 102206 The Second Hospital Affiliated To AMU \| Chongqing, Chongqing, China, 400037 The First Hospital Affiliated To AMU \| Chongqing, Chongqing, China, 400038 TheThird Affiliated Hospital ,Army Medical University \| Chongqing, Chongqing, China, 400042 The Second Affiliated Hospital of ChongQing Medical University \| Chongqing, Chongqing, China, 400060 Fujian Medical University Union Hospital \| Fuzhou, Fujian, China, 350001 The 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, 510060 Sun Yat-sen Memorial Hospital, Sun Yat-Sen University \| Guangzhou, Guangdong, China, 510220 NanFang Hospital of Southern Medical University \| Guangzhou, Guangdong, China, 510515 The first affiliated hospital of guangxi medical university \| Nanning, Guangxi, China, 530021 The Fourth Hospital of Hebei Medical University \| Shijiazhuang, Hebei, China, 050011 Harbin Medical University Cancer Hospital \| Harbin, Heilongjiang, China, 150000 Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology \| Wuhan, Hubei, China, 430022 Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology \| Wuhan, Hubei, China, 430030 Hunan Cancer Hospital \| Changsha, Hunan, China, 410006 Eastern Theater General Hospital, Qinhuai District Medical Area \| Nanjing, Jiangsu, China, 210002 The First Affiliated Hospital Of Nanchang University \| Nanchang, Jiangxi, China, 330006 Jilin Cancer Hospital \| Changchun, Jilin, China, 130000 The First Hospital of Jilin University \| Changchun, Jilin, China, 130000 The Sixth People's Hospital of Shengyang \| Shengyang, Liaoning, China, 110006 Liaoning Cancer Hospital \| Shenyang, Liaoning, China, 110042 Shandong Cancer Hospital Affiliated to Shandong University \| Jinan, Shandong, China, 250000 Fudan University Shanghai Cancer Center \| Shanghai, Shanghai, China, 200032 Zhongshan Hospital, Fudan University \| Shanghai, Shanghai, China, 200032 Shanghai Changhai Hospital \| Shanghai, Shanghai, China, 200043 West China Hospital of Sichuan University \| Chengdu, Si Chuan, China, 610041 Sichuan Cancer Hospital&Institute \| Chengdu, Sichuan, China, 610054 Sir Run Run Shaw Hospital \| Hangzhou, Zhejiang, China, 310016 ZheJiang Cancer Hospital \| Hangzhou, Zhejiang, China, 310022 The First Affiliated Hospital, Zhejiang University \| Hangzhou, Zhejiang, China, Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin \| Berlin, Germany, 13353 Pamela 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, 80147 Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS \| Bologna, Italy, 40138 Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) \| Brescia, Italy, 25123 Azienda Ospedaliero-Universitaria \| Cagliari, Italy, 09124 Azienda Ospedaliera Universitaria Careggi \| Firenze, Italy, 50134 Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico \| Milano, Italy, 20122 Fondazione Policlinico Universitario Agostino Gemelli IRCCS \| Roma, Italy, 00168 Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) \| Verona, Italy, 37134 Seoul National University Bundang Hospital Gyeonggi-do \| Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620 The Catholic University of Korea, St. Vincent's Hospital \| Suwon-si, Gyeonggi-do, Korea, Republic of, 16247 Ajou University Hospital \| Suwon, Gyeonggi-do, Korea, Republic of, 16499 Dong-A University Hospital \| Busan, Korea, Republic of, 602715 Korea University Anam Hospital \| Seoul, Korea, Republic of, 02481 Severance Hospital, Yonsei University Health System \| Seoul, Korea, Republic of, 03722 Asan Medical Center \| Seoul, Korea, Republic of, 05505 Samsung Medical Center \| Seoul, Korea, Republic of, 06351 Centrum Medyczne Pratia Gdynia \| Gdynia, Poland, 81338 Centrum Onkologii-Instytut im.M.Sklodowskiej Curie \| Gliwice, Poland, 44101 Pratia MCM Krakow \| Krakow, Poland, 30510 Przychodnia Med-Polonia Sp. z o.o. \| Poznan, Poland, 60693 Wielkopolskie Centrum Onkologii \| Poznan, Poland, 61866 Centrum Zdrowia MDM \| Warszawa, Poland, 00635 Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy \| Warszawa, Poland, 02034 NZOZ Centrum Badan Klinicznych \| Wroclaw, Poland, 51162 SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" \| Arkhangelsk, Russian Federation, 164045 SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine \| Chelyabinsk, Russian Federation, 454087 Irkutsk Regional Oncology Dispensary \| Irkutsk, Russian Federation, 664035 SBIH " Clinical Oncological Dispensary # 1" \| Krasnodar, Russian Federation, 350040 RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee \| Kursk, Russian Federation, 305035 "VitaMed" LLC \| Moscow, Russian Federation, 121309 SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement \| Moscow, Russian Federation, 143423 CJSC Avicenna \| Novosibirsk, Russian Federation, 630099 BHI of Omsk region "Clinical Oncology Dispensary" \| Omsk, Russian Federation, 644013 Pavlov First Saint Petersburg State Medical University \| Saint-Petersburg, Russian Federation, 197022 SPb SBIH "City Clinical Oncological Dispensary" \| Saint-Petersburg, Russian Federation, 197022 FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov" \| Saint-Petersburg, Russian Federation, 197758 SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan \| Ufa, Russian Federation, 450054 Hospital Universitario Reina Sofia \| Cordoba, Córdoba, Spain, 14004 Hospital Universitario Ramon y Cajal \| Madrid, Spain, 28034 Hospital Universitario Clinico San Carlos \| Madrid, Spain, 28040 Hospital Universitario 12 de Octubre \| Madrid, Spain, 28041 Hospital Universitario La Paz \| Madrid, Spain, 28046 Hospital Universitario HM Madrid Sanchinarro \| Madrid, Spain, 28050 Hospital Universitari i Politecnic La Fe \| Valencia, Spain, 46026 Changhua Christian Medical Foundation Changhua Christian Hospital \| Changhua, Taiwan, 500006 Chang Gung Memorial Hospital, Chiayi \| Chiayi City, Taiwan, 613 E-DA Cancer Hospital \| Kaohsiung, Taiwan, 82445 Kaohsiung Chang Gung Memorial Hospital \| Kaohsiung, Taiwan, 833 National Cheng Kung University Hospital \| Tainan, Taiwan, 704 National Taiwan University Hospital \| Taipei, Taiwan, 100 Taipei Veterans General Hospital \| Taipei, Taiwan, 11217 Chang Gung Memorial Hospital, Linkou \| Taoyuan, Taiwan, 333 Baskent University Adana Application and Research Center \| Adana, Turkey, 01229 Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital \| Ankara, Turkey, 06105 Ankara City Hospital \| Ankara, Turkey, 06800 Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty \| Istanbul, Turkey, 34098 Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital \| Istanbul, Turkey, 34147 Inonu Uni. Med. Fac. \| Malatya, Turkey, 44280 CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU \| Dnipro, Ukraine, 49102 Communal Non-profit Enterprise Regional Center of Oncology \| Kharkiv, Ukraine, 61070 CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection \| Kharkiv, Ukraine, 61166 Medical Center of Limited Liability Company Medical Center Concilium Medical \| Kyiv, Ukraine, 04050 Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council \| Lutsk, Ukraine, 43018 Communal Institution Odesa Regional Clinical Hospital \| Odesa, Ukraine, 65025 CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology \| Sumy, Ukraine, 40022 Zaporizhzhya 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 21, 2022
Documents Provided by Jiangsu HengRui Medicine Co., Ltd.: Statistical Analysis Plan April 19, 2022