A Study of SHR-1210 in Combination With Apatinib or Chemo... | NCT03092895

Label	Type	Description	Intervention Names
SHR-1210+Apatinib(Arm A）	Experimental		Biological: SHR-1210 Drug: Apatinib
SHR-1210+FOLFOX4 or GEMOX regimen(Arm B）	Experimental		Biological: SHR-1210 Drug: FOLFOX4 Drug: GEMOX

Name	Type	Description	Arm Group Labels	Other Names
SHR-1210	Biological	Subjects receive SHR-1210 intravenous at the dose 3mg/kg on Day 1 every 2 weeks	SHR-1210+Apatinib(Arm A） SHR-1210+FOLFOX4 or GEMOX regimen(Arm B）

Measure	Description	Time Frame
The Safety and Tolerability	The incidence of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03	Up to approximately 4 years

Measure	Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by investigator: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to approximately 4 years

Eligibility Module

Eligibility Criteria

Histologically confirmed advanced PLC or advanced BTC (including bile duct carcinoma and gallbladder carcinoma) ; not suitable to surgery or local regional treatment; with at least one measurable lesion per RECIST 1.1.
Arm A:Failed or intolerable to at least one prior systemic treatment for advanced PLC. Arm B:No previous systemic treatment for advanced PLC or BTC
ECOG Performance Status of 0 or1.
Child-Pugh Class A or B with 7 points .
Life Expectancy of at least 12 weeks.
Has controlled infection by Hepatitis B Virus (HBV DNA<500 IU/ml) or Hepatitis C Virus.
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 60 days for female subjects and 120 days for male subjects after the last dose of study drug.
Patient has given written informed consent.

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.
Known or evidence of abdomen fistula, gastrointestinal perforation, or abdominal abscess within the past 2 months.
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 > 140mmHg, diastolic blood pressure > 90 mmHg).
Factors to affect oral administration (such as patients unable to swallow oral medications, chronic diarrhea and ileus etc. situations evidently affect drug oral medication and absorption).
History of hepatic encephalopathy.
Known history of human immunodeficiency virus (HIV) infection.
Active infection or an unexplained fever > 38.5°C during screening visits.
Has received a live vaccine within 30 days.
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+ or 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. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily. prednisone equivalent, are permitted in the absence of active autoimmune disease
Any loco-regional therapy to liver (included but not limited: resection, radiotherapy, TAE, TACE, TAI, RFA or PEI) within 4 weeks prior to study.
Prior therapy with anti-PD-1 or other anti-PD-1/anti-PD-L1 immunotherapy.
Known history of hypersensitivity to monoclonal antibodies or any components of the study drugs.
Treatment with anti-coagulation therapy(Warfarin or heparin) or anti-platelet therapy(aspirin at dose≥300mg/day, clopidogrel at dose≥75mg/day).
Pregnant or breast-feeding women.
According to the investigator, other conditions that may lead to stop the research.

Facility	Status	City	State	ZIP	Country	Contacts
The Second Affiliated Hospital Of Anhui Medical University		Hefei	Anhui	230000	China
Hunan Cancer Hospital

PubMed Identifier	Type	Citation	Retractions
34309846	Derived	Chen X, Qin S, Gu S, Ren Z, Chen Z, Xiong J, Liu Y, Meng Z, Zhang X, Wang L, Zhang X, Zou J. Camrelizumab plus oxaliplatin-based chemotherapy as first-line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial. Int J Cancer. 2021 Dec 1;149(11):1944-1954. doi: 10.1002/ijc.33751. Epub 2021 Sep 8.
33741732	Derived

ID	Title	Description
FG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 12, 2018	Jul 4, 2023

ID	Title	Description
BG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
BG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.
BG002	Arm B：Cholangiocarcinoma（SHR-1210 + FOLFOX4 Q2W or SHR-1210 + GEMOX Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W：D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.
BG003	Arm B：Others	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W： D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00028 BG00134 BG00292 BG0033 BG004157

Type

Title

Description

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Reporting Status

Anticipated Posting Date

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Dispersion Type

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Calculate Percentage

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Arm/Group Information

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Analyses

Primary

The Safety and Tolerability

The incidence of adverse events (AEs) and Serious adverse events (SAEs) assessed by NCI-CTCAE v4.03

The primary safety endpoint was analyzed in SS. The SS included all participants who were treated .

Posted

Number

participants

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.
OG002	Arm B：Cholangiocarcinoma（SHR-1210 + FOLFOX4 Q2W or SHR-1210 + GEMOX Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W:D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.
OG003	Arm B：Others	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W:D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.

Units	Counts
Participants	OG00028 OG00134 OG00292 OG003

Title

Denominators

Categories

Number of Subjects with AEs

Title	Measurements
	OG00028 OG00134 OG00292 OG003

Secondary

Objective Response Rate (ORR)

Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by investigator: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210+ FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Duration of Response (DoR)

The time from the date of the first recorded objective tumor response (assessed as per RECIST V1.1) to the date of the first recorded objective tumor progression (assessed as per RECIST V1.1) or the date of death due to any cause, whichever occurs first, in subjects with a BOR of CR or PR.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Median

Full Range

months

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Disease Control Rate (DCR)

The percentage of subjects with a BOR of CR, PR, and SD as per RECIST V1.1. BOR of CR or PR must be confirmed at least 4 weeks (28 days) after the initial assessment.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Time to Progression (TTP)

The time from the date of the first dose to the date of radiographic PD (assessed by the investigator as per RECIST V1.1).PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or significant progression of non-target lesions leading to discontinuation of therapy, or the appearance of new lesions.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Median

95% Confidence Interval

months

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210+ FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Overall Survival

The time from the date of the first dose to death due to any cause. Overal Survial will be calculated based on Kaplan-Meier estimates

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Median

95% Confidence Interval

months

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Time to Response (TTR)

The time from the date of the first dose to the date of the first recorded tumor response (assessed as per RECIST V1.1) in subjects with a BOR of CR or PR.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Median

Full Range

months

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210+ FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Secondary

Progression-free Survival (PFS)

The time from the date of the first dose to the date of the first recorded tumor progression (assessed as per RECIST V1.1) or the date of death due to any cause, whichever occurs first.

The secondary efficacy endpoint was analyzed in FAS. The FAS included all participants who were treated.

Posted

Median

95% Confidence Interval

months

Up to approximately 4 years

ID	Title	Description
OG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.
OG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Hepatic failure	Hepatobiliary disorders	Systematic Assessment	EG0004 affected28 at risk EG0013 affected34 at risk EG0027 affected92 at risk EG0030 affected3 at risk
Hepatorenal failure	Hepatobiliary disorders	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Biliary obstruction	Hepatobiliary disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0003 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected28 at risk EG0011 affected34 at risk EG0025 affected92 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Multiple organ dysfunction syndrome	General disorders	Systematic Assessment	EG0003 affected28 at risk EG0014 affected34 at risk EG0027 affected92 at risk EG003
Disease progression	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG00210 affected92 at risk EG003
Pyrexia	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0027 affected92 at risk EG003
Asthenia	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Fatigue	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Death	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0024 affected92 at risk EG003
Herpes zoster	Infections and infestations	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Pneumonia	Infections and infestations	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0027 affected92 at risk EG003
Peritonitis	Infections and infestations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Biliary tract infection	Infections and infestations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Bacteraemia	Infections and infestations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Platelet count decreased	Investigations	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Hepatic enzyme abnormal	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Bilirubin conjugated increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0022 affected92 at risk EG003
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0021 affected92 at risk EG003
Blood bilirubin increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0022 affected92 at risk EG003
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0001 affected28 at risk EG0011 affected34 at risk EG0022 affected92 at risk EG003
Renal impairment	Renal and urinary disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 affected28 at risk EG0014 affected34 at risk EG0022 affected92 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0020 affected92 at risk EG003
Ascites	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0023 affected92 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Immune-mediated enterocolitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Gastrointestinal disorder	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Circulatory collapse	Vascular disorders	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Myelosuppression	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0021 affected92 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Facial paralysis	Nervous system disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Somnolence	Nervous system disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Depressed level of consciousness	Nervous system disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Reactive capillary endothelial proliferation	Immune system disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Hypersensitivity	Immune system disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Anaphylactic shock	Immune system disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0022 affected92 at risk EG003
Drug hypersensitivity	Immune system disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Eating disorder	Psychiatric disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Mental disorder	Psychiatric disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Acute myocardial infarction	Cardiac disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0006 affected28 at risk EG00113 affected34 at risk EG00245 affected92 at risk EG0030 affected3 at risk
Sinus tachycardia	Cardiac disorders	Systematic Assessment	EG0001 affected28 at risk EG0011 affected34 at risk EG0026 affected92 at risk EG003
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0008 affected28 at risk EG0015 affected34 at risk EG00214 affected92 at risk EG003
Hyperthyroidism	Endocrine disorders	Systematic Assessment	EG0002 affected28 at risk EG0012 affected34 at risk EG0024 affected92 at risk EG003
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0009 affected28 at risk EG0018 affected34 at risk EG00224 affected92 at risk EG003
Abdominal distension	Gastrointestinal disorders	Systematic Assessment	EG0005 affected28 at risk EG00110 affected34 at risk EG00225 affected92 at risk EG003
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0005 affected28 at risk EG0012 affected34 at risk EG00215 affected92 at risk EG003
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0005 affected28 at risk EG0017 affected34 at risk EG00240 affected92 at risk EG003
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0004 affected28 at risk EG00110 affected34 at risk EG00226 affected92 at risk EG003
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0004 affected28 at risk EG0019 affected34 at risk EG00225 affected92 at risk EG003
Stomatitis	Gastrointestinal disorders	Systematic Assessment	EG0004 affected28 at risk EG0011 affected34 at risk EG0027 affected92 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0003 affected28 at risk EG0014 affected34 at risk EG00213 affected92 at risk EG003
Ascites	Gastrointestinal disorders	Systematic Assessment	EG0003 affected28 at risk EG0017 affected34 at risk EG00211 affected92 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0003 affected28 at risk EG0011 affected34 at risk EG0027 affected92 at risk EG003
Intra-abdominal fluid collection	Gastrointestinal disorders	Systematic Assessment	EG0003 affected28 at risk EG0011 affected34 at risk EG0026 affected92 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Mouth ulceration	Gastrointestinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0024 affected92 at risk EG003
Noninfective gingivitis	Gastrointestinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Asthenia	General disorders	Systematic Assessment	EG00010 affected28 at risk EG0019 affected34 at risk EG00233 affected92 at risk EG003
Pyrexia	General disorders	Systematic Assessment	EG0009 affected28 at risk EG00110 affected34 at risk EG00256 affected92 at risk EG003
Chest discomfort	General disorders	Systematic Assessment	EG0003 affected28 at risk EG0011 affected34 at risk EG0024 affected92 at risk EG003
Face oedema	General disorders	Systematic Assessment	EG0002 affected28 at risk EG0011 affected34 at risk EG0028 affected92 at risk EG003
Oedema peripheral	General disorders	Systematic Assessment	EG0001 affected28 at risk EG0012 affected34 at risk EG00210 affected92 at risk EG003
Reactive capillary endothelial proliferation	Immune system disorders	Systematic Assessment	EG0006 affected28 at risk EG00126 affected34 at risk EG00257 affected92 at risk EG003
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG00023 affected28 at risk EG00122 affected34 at risk EG00253 affected92 at risk EG003
Platelet count decreased	Investigations	Systematic Assessment	EG00022 affected28 at risk EG00130 affected34 at risk EG00249 affected92 at risk EG003
Bilirubin conjugated increased	Investigations	Systematic Assessment	EG00020 affected28 at risk EG00115 affected34 at risk EG00218 affected92 at risk EG003
Blood bilirubin increased	Investigations	Systematic Assessment	EG00019 affected28 at risk EG00116 affected34 at risk EG00228 affected92 at risk EG003
White blood cell count decreased	Investigations	Systematic Assessment	EG00018 affected28 at risk EG00130 affected34 at risk EG00249 affected92 at risk EG003
Neutrophil count decreased	Investigations	Systematic Assessment	EG00017 affected28 at risk EG00129 affected34 at risk EG00244 affected92 at risk EG003
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG00015 affected28 at risk EG00114 affected34 at risk EG00243 affected92 at risk EG003
Gamma-glutamyltransferase increased	Investigations	Systematic Assessment	EG00010 affected28 at risk EG00110 affected34 at risk EG00237 affected92 at risk EG003
Weight decreased	Investigations	Systematic Assessment	EG00010 affected28 at risk EG0016 affected34 at risk EG00221 affected92 at risk EG003
Blood lactate dehydrogenase increased	Investigations	Systematic Assessment	EG0007 affected28 at risk EG0018 affected34 at risk EG00215 affected92 at risk EG003
Blood alkaline phosphatase increased	Investigations	Systematic Assessment	EG0006 affected28 at risk EG00113 affected34 at risk EG00235 affected92 at risk EG003
Haemoglobin decreased	Investigations	Systematic Assessment	EG0005 affected28 at risk EG0012 affected34 at risk EG0027 affected92 at risk EG003
Weight increased	Investigations	Systematic Assessment	EG0005 affected28 at risk EG0017 affected34 at risk EG0028 affected92 at risk EG003
Blood albumin decreased	Investigations	Systematic Assessment	EG0004 affected28 at risk EG0015 affected34 at risk EG0026 affected92 at risk EG003
Blood bilirubin unconjugated increased	Investigations	Systematic Assessment	EG0004 affected28 at risk EG0012 affected34 at risk EG0023 affected92 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	Systematic Assessment	EG0004 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Amylase increased	Investigations	Systematic Assessment	EG0003 affected28 at risk EG0017 affected34 at risk EG00210 affected92 at risk EG003
Hepatitis B DNA increased	Investigations	Systematic Assessment	EG0003 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Lipase increased	Investigations	Systematic Assessment	EG0003 affected28 at risk EG0019 affected34 at risk EG00219 affected92 at risk EG003
Albumin globulin ratio decreased	Investigations	Systematic Assessment	EG0002 affected28 at risk EG0012 affected34 at risk EG0023 affected92 at risk EG003
Blood creatinine increased	Investigations	Systematic Assessment	EG0002 affected28 at risk EG0011 affected34 at risk EG00210 affected92 at risk EG003
Blood glucose increased	Investigations	Systematic Assessment	EG0002 affected28 at risk EG0012 affected34 at risk EG0024 affected92 at risk EG003
Blood pressure increased	Investigations	Systematic Assessment	EG0002 affected28 at risk EG0011 affected34 at risk EG0025 affected92 at risk EG003
Urobilinogen urine increased	Investigations	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Blood potassium decreased	Investigations	Systematic Assessment	EG0001 affected28 at risk EG0012 affected34 at risk EG0024 affected92 at risk EG003
Neutrophil count increased	Investigations	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG0028 affected92 at risk EG003
Red blood cell count decreased	Investigations	Systematic Assessment	EG0001 affected28 at risk EG0013 affected34 at risk EG0025 affected92 at risk EG003
White blood cell count increased	Investigations	Systematic Assessment	EG0001 affected28 at risk EG0010 affected34 at risk EG00210 affected92 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	Systematic Assessment	EG00011 affected28 at risk EG00115 affected34 at risk EG00233 affected92 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0009 affected28 at risk EG00115 affected34 at risk EG00241 affected92 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0008 affected28 at risk EG0017 affected34 at risk EG00227 affected92 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0007 affected28 at risk EG00112 affected34 at risk EG00214 affected92 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0006 affected28 at risk EG0011 affected34 at risk EG0025 affected92 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 affected28 at risk EG0013 affected34 at risk EG00219 affected92 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 affected28 at risk EG0011 affected34 at risk EG0025 affected92 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG00210 affected92 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0008 affected28 at risk EG0013 affected34 at risk EG0024 affected92 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0007 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0006 affected28 at risk EG0014 affected34 at risk EG0028 affected92 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG0005 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG0003 affected28 at risk EG0013 affected34 at risk EG0026 affected92 at risk EG003
Hypoaesthesia	Nervous system disorders	Systematic Assessment	EG0001 affected28 at risk EG0017 affected34 at risk EG0026 affected92 at risk EG003
Insomnia	Psychiatric disorders	Systematic Assessment	EG0003 affected28 at risk EG0011 affected34 at risk EG0027 affected92 at risk EG003
Proteinuria	Renal and urinary disorders	Systematic Assessment	EG00014 affected28 at risk EG0017 affected34 at risk EG00213 affected92 at risk EG003
Haematuria	Renal and urinary disorders	Systematic Assessment	EG0005 affected28 at risk EG0014 affected34 at risk EG0026 affected92 at risk EG003
Pelvic fluid collection	Reproductive system and breast disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 affected28 at risk EG0013 affected34 at risk EG0026 affected92 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0010 affected34 at risk EG0023 affected92 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected28 at risk EG0012 affected34 at risk EG0021 affected92 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected28 at risk EG0015 affected34 at risk EG0020 affected92 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected28 at risk EG0011 affected34 at risk EG0026 affected92 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected28 at risk EG0011 affected34 at risk EG0025 affected92 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00011 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0004 affected28 at risk EG0014 affected34 at risk EG00211 affected92 at risk EG003
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0004 affected28 at risk EG0015 affected34 at risk EG00210 affected92 at risk EG003
Hypertension	Vascular disorders	Systematic Assessment	EG00022 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Varices oesophageal	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0013 affected34 at risk EG0022 affected92 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0020 affected92 at risk EG003
Influenza like illness	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0023 affected92 at risk EG003
Chills	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG00211 affected92 at risk EG003
Temperature intolerance	General disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0025 affected92 at risk EG003
Hypersensitivity	Immune system disorders	Systematic Assessment	EG0000 affected28 at risk EG0016 affected34 at risk EG00214 affected92 at risk EG003
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0000 affected28 at risk EG0013 affected34 at risk EG0027 affected92 at risk EG003
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0027 affected92 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected28 at risk EG0013 affected34 at risk EG0021 affected92 at risk EG003
Blood creatine phosphokinase increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0020 affected92 at risk EG003
Total bile acids increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0027 affected92 at risk EG003
Myoglobin blood increased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Neutrophil percentage decreased	Investigations	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0020 affected92 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0022 affected92 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected28 at risk EG0011 affected34 at risk EG0026 affected92 at risk EG003
Neurotoxicity	Nervous system disorders	Systematic Assessment	EG0000 affected28 at risk EG0013 affected34 at risk EG0021 affected92 at risk EG003
Dysphoria	Psychiatric disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0021 affected92 at risk EG003
Adnexa uteri mass	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0020 affected92 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected28 at risk EG0013 affected34 at risk EG0024 affected92 at risk EG003
Pigmentation disorder	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0020 affected92 at risk EG003
Haemorrhage subcutaneous	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected28 at risk EG0010 affected34 at risk EG0026 affected92 at risk EG003
Phlebitis	Vascular disorders	Systematic Assessment	EG0000 affected28 at risk EG0012 affected34 at risk EG0021 affected92 at risk EG003

ID	Term
C000631724	camrelizumab
C553458	apatinib
C410216	Folfox protocol

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A：SHR-1210+Apatinib	SHR-1210: 3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days. Apatinib mesylate: Orally administered, once daily, with four dose groups: 125 mg, 250 mg, 375 mg, and 500 mg, for dose exploration from low dose to high dose.	11	28	14	28	28	28
EG001	Arm B：Hepatocellular Carcinoma(SHR-1210 + FOLFOX4 Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks.	11	34	20	34	34	34
EG002	Arm B：Cholangiocarcinoma（SHR-1210 + FOLFOX4 Q2W or SHR-1210 + GEMOX Q2W)	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W： D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.	35	92	58	92	92	92
EG003	Arm B：Others	SHR-1210：3 mg/kg, intravenously infused within 30 min, not less than 20 min and not more than 60 min (including flushing time), once every 2 weeks. The interval between two doses must not be less than 12 days； FOLFOX4 regimen：D1: Oxaliplatin (OXA) 85 mg/m2 (2-h infusion) + calcium levofolinate (LV) 200 mg/m2 (2-h infusion), followed by 5-fluorouracil (5-Fu) 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion)，D2: LV 200 mg/m2 (2-h infusion), followed by 5-Fu 400 mg/m2 (bolus injection), and 5-Fu 600 mg/m2 (22-h infusion) Once every 2 weeks. GEMOX Q2W：D1: Gemcitabine (800 mg/m2, 80-min infusion) ，D2: Oxaliplatin (85 mg/m2, 2-h infusion) Once every 2 weeks.	1	3	2	3	3	3