Due to the rapid shifting of liver cancer disease landscape and the company's adjustment of development strategy.

This study consists of two parts: Phase I is a dose escalation study to determine the Recommended Phase II Dose (RP2D) of MGD013 monotherapy and that of MGD013 when in combination with Brivanib Alaninate (ZL-2301) in subjects with advanced liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma). Phase II is a dose expansion study and consists of two parts: Part 1 is to assess the safety and efficacy of MGD013 monotherapy and MGD013 in combination with ZL-2301 in subjects with advanced hepatocellular carcinoma (HCC); in Part 2, a therapeutic method (MGD013 monotherapy or MGD013 in combination with ZL-2301, determined by the sponsor according to the obtained data) will be selected for dose expansion study in HCC subjects who have previously failed immune checkpoint inhibitor treatment, to further evaluate the safety and efficacy of the study treatments in the specific group of subjects.

Inclusion Criteria:

1. Subjects who voluntarily sign the informed consent form (ICF);
2. Male or female subjects who are aged 18-75 years old;
3. Subjects with histologic, cytologic or clinical confirmed diagnosis of advanced HCC (Phase I could include intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma), and are not suitable for surgery or loco-regional therapy or have progressed following surgery and/or loco-regional therapy;
4. Subject who has at least one measurable lesion according to RECIST v1.1 criteria.
5. Phase I study: subjects who have previously received at least one line of systemic therapy, including immune checkpoint inhibitors, molecular targeted drugs or systematic chemotherapy, alone or in combination, and failed (progression confirmed by imaging) or were intolerant at the discretion of investigator; PhaseII：Advanced HCC cohort with subjects who have previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) prior one line immune checkpoint inhibitor treatment, including anti-PD-1 antibody/anti-PD-L1 antibody and / or anti-CTLA-4 antibody, and/or molecular targeted therapy or systematic chemotherapy (monotherapy or in combination); Phase II: Advanced HCC cohort with subjects who have not previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) or were intolerant to (at the discretion of investigator) previous molecular targeted therapy or systematic chemotherapy, without receiving immune checkpoint inhibitor treatment (including anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, and bispecific antibodies including the above targets).
6. Previous anti-tumor therapy must be completed no less than 2 weeks prior to the study treatment and all adverse events related to previous treatment must have recovered to CTCAE Grade ≤1; if subjects who have received prior immune checkpoint inhibitors have immune-related endocrinopathy, it should be controlled with hormone replacement therapy.
7. Phase I: Child-Pugh Class A; Phase II: Child-Pugh Class A or B with a score of ≤ 7;
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
9. Subjects with life expectancy ≥12 weeks;
10. Subjects with chronic HBV infection must have HBV-DNA <500 IU/ml, and have received at least 14 days of anti-HBV treatment (e.g. entecavir, tenofovir) prior to the initiation of study treatment and are willing to receive antiviral treatment throughout the study; Subjects with RNA-positive HCV must have received standard antiviral treatment and the elevation of their liver enzymes must not exceed the level of CTCAE Grade 1;
11. Adequate vital organ function as shown below:

(1) Blood system function (subjects must have not received blood transfusion or stimulating growth factors within 14 days prior to screening test): neutrophil count ≥1.5×109/L, platelet count ≥ 75×109/L, hemoglobin ≥ 90 g/L; (2) Liver and kidney function (no albumin transfusion within 14 days prior to screening test): serum total bilirubin ≤ 2.5×ULN, serum albumin ≥ 29 g/L, ALT and AST ≤ 5×ULN; serum creatinine <1.5×ULN or eGFR (Cockcroft-Gault formula) ≥ 60 ml/min; (3) Coagulation function: international normalized ratio (INR)≤2.3 or prothrombin time (PT) of ≤ 6 seconds above control; (4) Left ventricular ejection fraction (LVEF) ≥50% by two-dimensional echocardiography.

12. Female subjects (except for females who have underwent surgical sterilization and those have been menopausal for more than one year) who are of childbearing potential are required to adopt a medically proven method for contraception (e.g. intrauterine contraception device, contraceptive pill or condom) throughout the study and up to 120 days after the last dose of investigational products; females who are of childbearing age and who do not underwent surgical sterilization must have negative serum or urine HCG tests within 7 days prior to enrollment; female subjects must not be breastfeeding; male subjects whose partners are of childbearing potential should use effective contraceptive methods throughout the study and up to 120 days after the last dose of investigational product.

13. Subjects who are willing to provide oncological tissues (if applicable) for biomarker test.

Exclusion Criteria:

1. Subjects who have known fibrolamellar carcinoma of liver for phase I and subjects who have fibrolamellar carcinoma, mixed HCC- cholangiocarcinoma or cholangiocarcinoma for phase II;
2. Subjects with brain metastasis or leptomeningeal metastasis confirmed by brain MRI during screening period;
3. Subjects with a diagnosis of other malignant tumors within 5 years prior to first administration, except for skin basal cell carcinoma, skin squamous cell carcinoma and/or in situ cancer following radical resection;
4. Subjects who had liver or other sites loco-regional treatment (including transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), hepatic artery infusion (HAI), local radiotherapy, radioembolization, radiofrequency ablation, cryoablation or percutaneous ethanol injection) , or who had major surgery of liver or other sites within 4 weeks prior to first administration, or had minor surgical procedures (e.g. simple excision, tooth extraction) within one week prior to first administration, or had received palliative radiotherapy for bone metastasis within 2 weeks and radiotherapy-related toxicity ≥ CTCAE Grade 2.
5. Subjects who have moderate or severe ascites (detected by B-ultrasound or CT), or require therapeutic abdominal paracentesis or drainage;
6. Subjects with a history of hepatic encephalopathy;
7. Subjects with a history of unhealed wounds or ulcers or bone fractures within 3 months prior to study enrollment;
8. Subjects who plan to have or had allogenic organ or bone marrow transplantation;
9. Subjects who are at increased risk of bleeding or have history of thrombosis:

(1) Clinically significant bleeding within 3 months prior to screening or clear bleeding tendency; (2) Gastrointestinal hemorrhage within 6 months prior to screening or clear tendency of gastrointestinal hemorrhage; (3) Arterial/venous thromboembolic events within 6 months prior to screening, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, etc.; (4) Require anticoagulation therapy with an agent such as warfarin or heparin; (5) Require chronic anti-platelet therapy (such as aspirin≥100 mg/day, clopidogrel, etc.); 10. Subjects who have clinically significant cardiovascular diseases:

1. NYHA (New York Heart Association)stage 3 and 4 congestive heart failure;
2. Unstable angina pectoris or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to screening;
3. Arrhythmias requiring medications other than β-blockers;
4. Valvular heart disease of ≥ CTCAE grade 2;
5. Hypertension inadequately controlled by drugs (systolic pressure >150 mmHg or diastolic pressure >90 mmHg); 11. Subjects who have history of symptomatic pulmonary fibrosis, or have interstitial pneumonitis, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severe impairment of pulmonary function, or other suspicious pulmonary diseases that may interfere with drug-related pulmonary toxicity detection and treatment; 12. Subjects who have suffered active bacterial or fungal infections requiring systemic treatment within 7 days prior to screening; or active tuberculosis; 13. Subjects with active co-infection of Hepatitis B and C, confirmed by positive HBV surface antigen or HBV DNA and HCV RNA 14. Subjects who have any active, known or suspected autoimmune disease; 15. Subjects with a condition requiring systematic treatment with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within 14 days before administration of the investigational drug. In the absence of active autoimmune diseases, inhalation or topical use of steroids (>10 mg/day prednisone or equivalent) is allowed; 16. Other laboratory abnormalities:

(1) Hyponatremia, hypokalemia or hypophosphatemia that have occurred before the first administration, and failed to restore to normal level after electrolyte supplementation therapy; (2) Confirmed diagnosis of thyroid dysfunction, which cannot be maintained within normal range following thyroid hormone replacement therapy; (3) Positive Human immunodeficiency virus (HIV) test; 17. QTc interval >480 ms on two consecutive ECGs; 18. Female subjects during pregnancy or lactation; female subjects of childbearing potential or male subjects who are not willing to use contraception or contraceptive measures during the study; 19. Subjects who have previously received two lines and above tumor immune checkpiont inhibitor treatment, mainly including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, etc, or bispecific antibodies including the above targets, or received anti-LAG-3 antibody; whether subjects who have previously received other tumor immunotherapy can be enrolled should be determined by the sponsor; 20. Known or suspected history of severe allergy to investigational drugs; 21. Subjects who have received live attenuated vaccines or any investigational drugs that have not been marketed in China within 4 weeks prior to first administration; 22. If subjects who have previously used immune checkpoint inhibitors (such as anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies) have the following drug-related adverse events, they will be not suitable for inclusion regardless of recovered or not:

1. ≥ Grade 3 eye-related adverse events
2. Grade 4 abnormal liver function
3. ≥ Grade 3 neurotoxicity
4. ≥ Grade 3 colitis
5. ≥ Grade 3 renal toxicity
6. ≥ Grade 3 pneumonitis 23. Subjects who are not suitable for inclusion as judged by the investigators.