A Trial of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With FOLFOX4 in Subjects With Advanced HCC Who Have Never Received Prior Systemic Treatment.

A Phase III, Multicentered, Randomized, Double-blinded, Parallel Controlled Study to Evaluate Camrelizumab (PD-1 Antibody) in Combination With FOLFOX4 Regimen Versus Placebo in Combination With FOLFOX4 Regime in First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC).

The study is being conducted to evaluate the efficacy and safety of SHR-1210 plus FOLFOX4 in subjects with advanced HCC who have never received prior systemic treatment compared to placebo plus FOLFOX4.

The primary study hyposis is that Camrelizumab combined with FOLFOX4 treatment can improve Overall Survival when compared with placebo in combination with FOLFOX4 Regimen.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: SHR-1210; Drug: FOLFOX4; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 396
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Linna Wang, MD; Phone Number: 021-60453196; Email: wanglinna@hrglobe.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • Recruiting
      • 81 Hospital Nanjing
      • Contact: Shukui Qin, MD; Phone Number: +862580864542

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Has not received prior systemic treatment for their advanced/metastatic HCC. Has measurable disease according to RECIST v1.1. ECOG Performance Status of 0 or 1. Child-Pugh Class A or B with 7 points. Life Expectancy of at least 12 weeks. HBV DNA<500 IU/ml. Adequate organ function： Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion Criteria:

Known fibrolamellar HCC, Prior malignancy active with the previous 5 years except for locally curable cancers that have been apparently cured.

Known or occurrence of central nervous system (CNS) metastases. Ascites with clinical symptoms. Known or evidence of GI hemorrhage within the past 6 months. Known or occurrence of hemorrhage/ thrombus. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias.

Grade III~IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%.

Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 150mmHg, diastolic blood pressure > 90 mmHg).

History of hepatic encephalopathy. Known history of human immunodeficiency virus (HIV) infection. Active infection or an unexplained fever > 38.5°C during screening visits. Prior or planning to organ transplantation including liver transplantation. Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity.

Proteinuria≥ 2+ and 24 hours total urine protein > 1.0 g. Active known, or suspected autoimmune disease. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment.

Any loco-regional therapy to liver (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks prior to study.

Known history of hypersensitivity to monoclonal antibodies or any components of the study drugs.

Pregnant or breast-feeding women. According to the investigator, other conditions that may lead to stop the research.

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: SHR-1210; SHR-1210+FOLFOX4	Drug: SHR-1210; Subjects receive SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 2 weeks; Drug: FOLFOX4; Subjects receive FOLFOX4 treatment on D1-D2 of every 2 weeks
Experimental: CONTROL; SHR-1210+Placebo	Drug: FOLFOX4; Subjects receive FOLFOX4 treatment on D1-D2 of every 2 weeks; Drug: Placebo; Subjects receive placebo of SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS was defined as the time from randomization to death due to any cause	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per RECIST 1.1 in all participants	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	Up to approximately 6 months
Time to Progression (TTP) per RECIST 1.1 in all participants		Up to approximately 3 years
Duration of Response (DoR) per RECIST 1.1 in all participants		Up to approximately 3 years
Disease Control Rate (DCR) per RECIST 1.1 in all participants		Up to approximately 3 years
Progression-free Survival (PFS) per RECIST 1.1 in all participants		Up to approximately 3 years
AE		Up to approximately 3 years
Overall Survival (OS) rate at 9 months and 12 months		Up to approximately 9 months and 12 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Chair: Shukui Qing, MD, China, Jiangsu 81 Hospital Nanjing

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 22, 2018
• First Submitted That Met QC Criteria: July 22, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

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
• Other Study ID Numbers: SHR-1210-III-305-HCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No