Assessment of Safety ,Tolerance and Pharmacokinetics Clinical Efficacy With BAT4706 in Advanced Solid Tumors

Inclusion Criteria:

• Age 18 to 75 years old (including boundary value), male or female;
• Voluntarily sign informed consent;
• Study population: advanced patients diagnosed by pathology and without effectivestandard treatment or standard treatment failure or standard treatment intolerance orrefuse standard treatment.Patients with malignant solid tumors. (the extended studyphase is mainly for patients with advanced melanoma);
• According to recist1.1 standard, there is at least one measurable tumor focus;
• ECOG score shall be 0 or 1;
• The investigator assessed the expected survival ≥ 12 weeks;
• Have sufficient organ and bone marrow functions as below:Blood routine (no bloodtransfusion, no hematopoietic stimulator, and no medication to correct blood countwithin 14 days prior to first dosing),Neutrophil absolute count (ANC) ≥1.5×109 /L,Platelet count ≥75×109/L, Hemoglobin ≥90g/L, Blood coagulation function Prothrombintime (PT) or International standardized ratio (INR) and activated partial thrombintime (APTT) ≤ 1.5×ULN, Liver function Total bilirubin (TBIL) ≤2×ULN ,Alanineaminotransferase (ALT), aspartate aminotransferase (AST) -- ≤3×ULN,Serum Creatinine ≤1.5×ULN ，renal function Serum creatinine clearance rate & GT; 60ml/min (Cockcroft-Gault formula, see appendix)
• Female patients with fertility must have negative serum pregnancy test duringscreening, and agree to take effective birth control / contraception to preventpregnancy from the study period to 6 months after the last administration. Malepatients must agree to take effective contraceptive methods from the study period to 6months after the last administration.

Exclusion Criteria:

• Have received experimental drug treatment or participated in clinical research ofmedical devices within 4 weeks before the first administration of study drugsResearch;
• Received chemotherapy, radiotherapy, Biological therapy, endocrine therapy,immunotherapy, and other anti-tumor treatments within 4 weeks before the firstadministration of the study drug, except: 1. Nitrosourea or mitomycin C within 6 weeksprior to the first use of the study drug. 2. Oral fluorouracil and small moleculetargeted drugs within 2 weeks or 5 half lives,Whichever is longer, etc.). 3.Traditional Chinese medicine/traditional Chinese patent medicines with definiteanti-tumor effect, and drugs with immunomodulatory effect (including but not limitedto thymosin Interferons, interleukins, etc.) within 2 weeks prior to the first use ofthe study drug. 4. Palliative radiotherapy within 2 weeks prior to the first use ofthe study drug.
• Failure of CTLA-4 monoclonal antibody treatment in the past;
• Before the first administration of the study drug, the AE (ctcae5.0) caused byprevious antitumor treatment was still > grade 1, hair loss and menstrual stimulationExcept those with stable immune hypothyroidism controlled by hormone replacementtherapy;
• Received interventional therapy and major surgery (such as craniotomy, thoracotomy orlaparotomy) within 4 weeks before the first administration of the study drug;Surgeryis defined here as grade 3 and 4 surgery;
• Have a history of organ transplantation;
• Central nervous system or meningeal metastasis;
• If other malignant tumors have been diagnosed in recent 5 years, or the previousmalignant tumors have been cured for less than 5 years, the time of the firstpathological diagnosis shall prevail Subject to. Except for radical skin basal cellcarcinoma, cutaneous squamous cell carcinoma or in situ carcinoma, such as in situbreast cancer, Cervical carcinoma in situ);
• Patients with ocular melanoma;
• Patients with esophageal or gastric variceal bleeding in the past 6 months, or theinvestigator assessed the risk of bleeding;
• Serious cardiovascular disease occurred within 6 months before the first medication:the New York Heart Association rating (NYHA) is 2 Heart failure of grade and above,left ventricular ejection fraction (LVEF) < 50%, unstable arrhythmia or unstable heartColic and uncontrollable hypertension (this protocol is defined as contraction aftertreatment despite optimal antihypertensive treatment Blood pressure > 150mmhg and / ordiastolic blood pressure > 100mmhg, and the investigator's evaluation is of clinicalsignificance);
• Patients with a history of autoimmune diseases; Had splenectomy or splenicirradiation;
• Drugs with immunomodulatory effect (e.g. thymosin, interferon, interleukin) were usedwithin 2 weeks before the first administration of the study drug Hormone) or hormone (equivalent dose > prednisone 10mg / day);
• Untreated or under treatment tuberculosis patients, including but not limited totuberculosis; Those who have received standardized anti-tuberculosis treatment andhave been confirmed by researchers as cured can be included;
• Patients who have experienced severe infections within 4 weeks prior to the firstmedication use, including but not limited to infection complications requiringhospitalization, bacteremia, severe pneumonia, etc; Exclude patients with activeinfections before the first administration;
• Patients with a history of non infectious pneumonia requiring glucocorticoid treatmentor current interstitial lung disease within one year before the first administration;
• Patients with uncontrolled or requiring drainage of pleural effusion, pericardialeffusion, or abdominal effusion;
• Individuals with the following risks of thrombosis or bleeding:

1. Have experienced myocardial infarction, unstable angina pectoris, cerebrovascularaccident, or transient ischemic attack within 6 months before the firstadministration;
2. A history of deep venous thrombosis, pulmonary embolism, or any other severethromboembolism within 3 months prior to the first administration (implantablevenous infusion port or catheter derived thrombosis, or superficial venousthrombosis is not considered "severe" thromboembolism);
3. Any life-threatening bleeding event or grade 3 or 4 gastrointestinal/varicealbleeding event requiring blood transfusion, endoscopy, or surgical treatmentwithin 3 months prior to the first administration;
4. Investigator believe that other diseases with a higher risk of bleeding orthrombosis in the future

• Patients with active tuberculosis; Active infections requiring intravenous antibiotictreatment;
• People infected with the following diseases: human immunodeficiency virus (HIV)infection; Treponema pallidum antibody positive; hepatitis B virus Infected personswere positive for hepatitis B surface antigen (HBsAg) and hepatitis B virusdeoxyribonucleic acid (HBV DNA) detection > 2000iu / ml (or 1 × 104 copies / ml); HCVinfected persons [HCV antibody and disease];Viral RNA (HCV RNA) test results werepositive];
• Inoculated within 4 weeks before the first medication, or planned to receive live /attenuated vaccine during the study period;
• Known hypersensitivity to any monoclonal antibody;
• Known history of psychotropic substance abuse or drug abuse;
• Pregnant or lactating women;
• Other patients considered by the investigator as unsuitable to participate in thisstudy.