An Open-label Phase I/II Clinical Trial of PT-112 Injection for Advanced Solid Tumors and Advanced Hepatocellular Carcinoma

Inclusion Criteria:

• Age ≥ 18 years old and ≤ 75 years old, male or female

• Local advanced or metastatic solid tumors confirmed by histopathology or cytology thatdo not respond to standard treatment or have no standard effective treatment (including but not limited to hepatocellular carcinoma, gastric cancer, colorectalcancer, non-small cell lung cancer, head and neck cancer, and breast cancer)

• Compliance with the requirements for type of tumor in the group in dose confirmationstage;

• Eastern Cooperative Oncology Group (ECOG) physical score: 0 or 1

• Lesions that can be assessed by imaging according to the Response evaluation criteriain solid tumors (RECIST) 1.1 (not required in dose escalation stage);

• Expected survival>12 weeks;

• Subjects should have appropriate organ function and should meet the followingrequirements for laboratory test results before inclusion: Generally normal bone marrow reserve: absolute neutrophil count (ANC)

≥1.510^9/L, platelet count≥10010^9/L and hemoglobin≥90 g/L; Generally normal liverfunction: serum albumin ≥3.0 g/dL; bilirubin ≤1.5×upper limits of normal (ULN), Alanineaminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5×ULN, ALT or AST ≤5×ULNfor patients with liver metastases or primary liver cancer; Normal renal function:creatinine ≤1.5×ULN or creatinine clearance ≥60ml/min (according to Cockcroft-Gaultformula); Generally normal coagulation function: International NormalizedRatio(INR)≤1.5×ULN, activated partial thromboplastin time (APTT) ≤1.5×ULN; Cardiacfunction: Left ventricular ejection fraction (LVEF)≥ 50%;

• Women of childbearing age (defined as women under 50 years old or above 50 years oldwho have an amenorrhea period shorter than 12 months before inclusion in the study)who show negative in serum β-human chorionic gonadotrophin (β-HCG) test;

• Subjects with history of brain metastases who are diagnosed with stable disease notrequiring treatment with steroid or anticonvulsant, regardless of previousradiotherapy;

• Signing of informed consent form before participation in the study. Other inclusion criteria for the phase II trial:

• Advanced HCC diagnosed by histopathology or cytology that cannot be surgically removedor progresses after intervention/local treatment, previous treatment with one systemicanti-cancer chemotherapy, Barcelona Clinic Liver Cancer (BCLC) staging: Stage C,Child-Pugh A and mild grade B (≤7);

• Lesions that can be assessed by imaging according to the RECIST 1.1;

Exclusion Criteria:

• Untreated active hepatitis (hepatitis B: HBsAg positive with abnormal liver functionand hepatitis B virus(HBV)-DNA ≥ 2000international unit (IU)/ml; hepatitis C:hepatitis C virus (HCV)-RNA positive and abnormal liver function);

• antitumor immunoregulation therapy, immunosuppressive therapy, corticosteroids > 20mg/day (unless used to prevent contrast agent reactions during radiotherapy), growthfactor therapy (such as erythropoietin) or transfusion therapy within 14 days beforeuse of the investigational drug;

• Unrecovered toxic and side effects caused by previous treatment (CTCAE ≤ grade 1),except hair loss and other tolerable events judged by the investigators;

• Any grade of peripheral neuropathy within 28 days prior to use of the investigationaldrug;

• Known allergy or hypersensitivity to platinum drugs;

• Antitumor therapy like chemotherapy, biotherapy, radiotherapy, endocrine therapy,target therapy (except Nitrourea, mitomycin C) within 4 weeks before use of theinvestigational drug. Use Nitrourea or mitomycin C within 6 weeks before use of theinvestigational drug.

• Major surgery within 28 days before use of the investigational drug;

• Acute bacterial, viral or fungal infections requiring systemic treatment orunexplained fever during screening before the first administration of drug (bodytemperature> 38.5℃);

• Moderate or massive effusion of body cavity need treatment;

• History of mental illness;

• Human Immunodeficiency Virus(HIV) carriers or Acquired Immune Deficiency Syndrome (AIDS) patients;

• Any of the following conditions within six months before sign informed consent form :uncontrolled congestive heart failure (New York Heart Association grade 2 or 4),angina pectoris, myocardial infarction, stroke (except lacunar infarction),coronary/peripheral artery bypass surgery, pulmonary embolism);

• Uncontrolled arrhythmia or persistent QT interval prolongation, > 450 ms for men or > 470 ms for women;

• Use of any investigational drug or device within 28 days before the use ofinvestigational drug;

• Pregnant or lactating women;

• Women of childbearing age and fertile men who cannot take effective adequate doublecontraceptives during the study or within three months after completion of the study;

• Any other conditions based on which the investigators believe that the patient shouldnot participate in the study; Other exclusion criteria for the phase II trial:

• Patients with advanced HCC who have received more than two kinds of systemicchemotherapy (but not including targeted therapies or immunity checkpoint inhibitorslike programmed death(PD)-1 or PD-L1 antibody treatment).