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

Conditions

Locally Advanced or Metastatic and Unresectable HCC

Brief 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.

Stephen Lam Chan, Ahmed Omar Kaseb, Laura Alexander, Xianzhang Meng, Kristin Ryan et al. (7 authors)

Liver Cancer2026-02-23

10.1159/000551156

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.

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.

2025-12-01

10.1016/s1470-2045(25)00543-1

Clinical outcomes of camrelizumab + rivoceranib vs sorafenib (CARES-310) as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC) of non-viral and viral etiology.

Rachna T. Shroff, Wei Shi, Xiu‐Zhi Wu, Xianzhang Meng, M. Maj et al. (8 authors)

Journal of Clinical Oncology2025-01-272 citations

10.1200/jco.2025.43.4_suppl.578

Camrelizumab plus rivoceranib vs sorafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Final overall survival analysis of the phase 3 CARES-310 study.

Arndt Vogel, Stephen L. Chan, Zhenggang Ren, Yuxian Bai, Shanzhi Gu et al. (21 authors)

Journal of Clinical Oncology2024-06-0130 citations

10.1200/jco.2024.42.16_suppl.4110

Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.

Adam M. Burgoyne, Ahmed O. Kaseb, Wei Shi, Laura E. Crotty Alexander, Xianzhang Meng et al. (10 authors)

Journal of Clinical Oncology2024-06-011 citations

10.1200/jco.2024.42.16_suppl.e16197

Impact of baseline liver function on survival outcomes in patients with unresectable hepatocellular carcinoma (uHCC) treated with camrelizumab + rivoceranib vs sorafenib: A post hoc analysis of study CARES-310.

Arndt Vogel, Ann‐Lii Cheng, Wei Shi, Seong Ho Jang, Laura E. Crotty Alexander et al. (8 authors)

Journal of Clinical Oncology2024-01-204 citations

10.1200/jco.2024.42.3_suppl.509

Patient-reported outcomes (PROs) <65 or ≥ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

Stephen L. Chan, Ahmed O. Kaseb, Wei Shi, Laura E. Crotty Alexander, Xianzhang Meng et al. (8 authors)

Journal of Clinical Oncology2024-01-202 citations

10.1200/jco.2024.42.3_suppl.456

Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study.

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.

2023-07-24472 citations

10.1016/s0140-6736(23)00961-3

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects

Ting Li, Xin Li, Xin Jiang, Chenjing Wang, Feifei Sun et al. (12 authors)

Cancer Chemotherapy and Pharmacology2022-09-153 citations

10.1007/s00280-022-04474-8

Antibodies to watch in 2020.

Kaplon H, Muralidharan M, Schneider Z, Reichert JM.

2020-01-01328 citations

10.1080/19420862.2019.1703531

Interventions

DRUGSHR-1210

Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial

DRUGApatinib

Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet

DRUGSorafenib

Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.

Countries

Belgium, China, Germany, Hong Kong, Italy, Poland, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States

Participant flow

Participants by arm

Arm	Count
Camrelizumab+Rivoceranib Arm Camrelizumab+rivoceranib arm: Rivoceranib 250 mg orally, QD, within 30 minutes after a meal, continuously. Camrelizumab 200 mg IV infusion, over 30 minutes, Q2W. The interval between two doses should not be less than 12 days.	272
Sorafenib Arm Sorafenib arm: Sorafenib 400 mg orally, BID, in a fasted state (at least 1 hour before or 2 hours after a meal), continuously.	271
Total	543

Baseline characteristics

Characteristic	Camrelizumab+Rivoceranib Arm	Sorafenib Arm	Total
Age, Customized <65 Years	191 participants	210 participants	401 participants
Age, Customized >=65 Years	81 participants	61 participants	142 participants
Race/Ethnicity, Customized Asian	226 Participants	224 Participants	450 Participants
Race/Ethnicity, Customized Black Or African American	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Other	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized White	44 Participants	46 Participants	90 Participants
Sex: Female, Male Female	45 Participants	41 Participants	86 Participants
Sex: Female, Male Male	227 Participants	230 Participants	457 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	34 / 272	17 / 269
other Total, other adverse events	268 / 272	262 / 269
serious Total, serious adverse events	114 / 272	49 / 269