Study of the Combination of CM082 With JS001 in Patients With Advanced Mucosal Melanoma.

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of recurrence after surgery,inoperable resection or metastasis advanced mucinous melanoma (III/IV period).

• Has not received any systemic anti-tumor medication (previously adjuvant orneoadjuvant therapy is required, but the treatment should be completed for at least 4weeks prior to the first dose of study drug, and all related toxicity events havereturned to normal or no more than Grade I of CTCAE 4.03, except for hair loss).

• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.

• Life expectancy of at least 12 weeks.

• All patients should provid tumor tissue specimens (preferably fresh tissue specimens)for PD-L1 expression analysis prior to enrollment.

• There is at least one measurable lesion according to the RECIST 1.1 standard and thelesion has not received radiotherapy.

• Patients may have a history of brain/mesis metastases, but must undergo topicaltreatment(surgery/radiotherapy) and be clinically stable for at least 3 months priorto the start of the study .If orticosteroids have been used before, they should bediscontinued for at least 2 weeks before the first dose of study drug.

• The level of organ function must meet the following requirements (7 days before thefirst dose of study drug):

• Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L, platelet (PLT) ≥ 100 × 109 / L, hemoglobin (HB) ≥ 9g / dL (no blood transfusion or receiving bloodcomponents within 14 days before detection);

• Liver: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal（ULN）,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5*ULN (ifliver metastasis, AST, ALT allowed) ≤ 5 *ULN);

• Serum creatinine ≤ 1.5*ULN and endogenous creatinine clearance ≥ 50mL / min (Cockcroft-Gault formula);

• Well-controlled hypertensive patients can be enrolled;

• International normalized ratio (INR), activated partial thromboplastin time (aPTT) ≤ 1.5 *ULN for patients who have not received anticoagulant therapy;patients who receive anticoagulant therapy should be treated within therequirements of label

• Urine protein ≤ 1+, if urine protein > 1+, 24 hours urine protein measurement isrequired, the total amount of which needs ≤ 1 gram;

• FT3, FT4, TSH normal or abnormal has no clinical significance;

• The heart function is normal, that is, the electrocardiogram is normal orabnormal has no clinical significance. The echocardiography shows that the leftventricular ejection fraction (LVEF) is greater than 50%.

• Serum pregnancy test results must be negative within 7 days prior to the first dose ofthe test drug for women of childbearing age; males with fertility or women who are atrisk of pregnancy must use highly effective methods of contraception throughout thetrial (eg oral contraceptives, pIntrauterine device, controlled libido or barriercontraceptive method combined with spermicide), and continued contraception for 12months after the end of treatment.

• Ability to understand the nature of this trial and give written informedconsent.Willingness and ability to comply with trial and follow-up procedures

Exclusion Criteria:

• Patients who have previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, orVEGFR TKI therapy.

• Patients currently receiving anti-tumor treatment

• Patients who participated in or were participating in other drug/therapy clinicaltrials within 4 weeks prior to the first dose of the study drug.

• Patients who received large surgery within 4 weeks before the first dose of the testdrug or has not recovered from the side effects of this operation, received livevaccination or immunotherapy within 4 weeks before the first dose of the test drug,and radiotherapy was performed within 2 weeks. In the past 5 years, there have been history of malignant tumors other than mucosalmelanoma, except for cured skin basal cell carcinoma, cutaneous squamous cell carcinoma,early prostate cancer, and cervical carcinoma in situ.

• Hematopoietic stimulating factors were received within 1 week prior to the first doseof the study drug, such as granulocyte colony-stimulating factor (G-CSF) anderythropoietin.

• HIV antibody or Treponema pallidum antibody test results are positive.

• If HBsAg or HBcAb is positive, HBV DNA should be tested.Patients should be excluded ifthe measurement is above the upper limit of the normal range.If HCV antibody ispositive, HCV DNA should be tested.Patients should be excluded if the measurement isabove the upper limit of the normal range.

• Those known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs andtheir components; those known to be allergic to CM-082 and any of its excipients.

• A large amount of pleural or ascites with clinical symptoms and requiring symptomatictreatment.

• Active lung disease (eg, interstitial pneumonia, pneumonia, obstructive pulmonarydisease, asthma) or a history of active tuberculosis.

• Have any clinical problems out of control, including but not limited to:

• Persistent or active (severe) infection;

• Hypertension that is not effectively controlled (blood pressure lasts greaterthan 150/90mmHg);

• Diabetes that is not effectively controlled;

• Heart disease, defined as grade III/IV congestive heart failure or heart blockdefined by the New York Heart Association

• Having a history of or suspected of having an autoimmune disease;Having a historyof any kind of disease requiring treatment with a steroid/immunosuppressive, suchas: pituitary inflammation, colitis, hepatitis, nephritis, hyperthyroidism,Hypothyroidism, etc.;

• The following situation occurred within 6 months before the first dose:

• Deep vein thrombosis or pulmonary embolism;

• myocardial infarction;

• severe or unstable arrhythmia or angina;

• percutaneous coronary intervention, acute coronary syndrome, coronary arterybypass grafting;

• Cerebrovascular accident, transient ischemic attack, and cerebral embolism.

• The patient has any condition that affects the swallowing of the drug, as well as anyconditions that affect the course of treatment (absorption, distribution, metabolism,or excretion) of the test drug, including any type of gastrointestinal resection orsurgical history.

• Have received a stem cell transplant or an organ transplant.

• Has a history of psychotropic substance abuse which is unable to quit or has a historyof mental disorders.

• Patients who need to use during the study or have used or the following drugs within 14 days prior to the first dose: CYP3A4 strong inhibitor or strong inducer; warfarinor any other coumarin derivative anticoagulant.

• The investigator judges other severe, acute or chronic medical illness or laboratoryabnormalities that may increase the risk associated with the study or may interferewith the interpretation of the findings.

• The investigator judged that the patient's compliance was poor or that there wereother conditions that were not suitable for the trial.