A Study of Anlotinib and AK105 Injection in Subjects With Gastrointestinal Tumors, Urinary System Tumors, Neuroendocrine Tumors

Inclusion Criteria:

* 1\. Cohort 1：Histopathologically confirmed metastatic or inoperable cholangiocarcinoma failed with first-line or above chemotherapy.

Cohort 2： Histopathologically confirmed recurrent or metastatic colorectal cancer that is not suitable for surgery with MSI-H or dMMR.

Cohort 3： Histopathologically confirmed metastatic or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Cohort 4：Histopathologically confirmed local progression or metastatic urothelial carcinoma that is not suitable for surgery.

Cohort 5：Low- and medium-grade (G1 or G2) late gastrointestinal pancreatic neuroendocrine tumor (NET) subjects diagnosed by pathology." 2.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.

3.At least one measurable lesion. 4.The main organs function are normally. 5. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.

6\. Understood and signed an informed consent form.

Exclusion Criteria:

* 1.Has used anti-angiogenic drugs such as bevacizumab, erlotinib, apatinib, sorafenib, sunitinib, and endothelium or against PD-1, PD-L1 and other related immunotherapeutic drugs.

  2\. HER2 positive in cohort 3. 3. Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose.

  4.Has brain metastases with symptoms or symptoms control for less than 2 months.

  5.Has diagnosed and/or treated additional malignancy within 5 years prior to the first dose.

  6.Has multiple factors affecting oral medication. 7.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

  8.Has unrelieved spinal cord compression. 9.Imaging shows that tumors invade large blood vessels. 10.Has hemoptysis within 1 month prior to the first dose and maximum daily hemoptysis ≥2.5 mL.

  11.Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1.

  12.Has received surgery, or unhealed wounds within 4 weeks before the first dose.

  13\. Has artery/venous thrombosis prior to the first dose within 6 months. 14. Has drug abuse history that unable to abstain from or mental disorders 15. Has any serious and / or uncontrolled disease. 16. Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose.

  17.Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components.

  18\. Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage \> 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first dose.

  19.Diagnosed as immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose \>10 mg/day of prednisone or other therapeutic hormones) and continued to be used for 2 weeks prior to the first dose 20. Has participated in other anticancer drug clinical trials within 4 weeks. 21. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.