Study of AK105 With Anlotinib and Radiotherapy Adjuvant Therapy in MGMT Unmethylated Newly Diagnosed Glioblastoma.

Inclusion Criteria:

* The patient voluntarily joined the study and signed a written informed consent;
* Pathologically confirmed treatment-naïve glioblastoma with PCR tested MGMT unmethylated;
* The interval between the last biopsy or surgery is 4-6 weeks, and the surgical incision is healed well;
* According to Rano criteria, there are evaluable measurable disease;
* 18-70 years of age;
* Karnofsky performance status (KPS) ≥ 60; and estimated survival of at least 3 months;
* The main organ function to meet the following criteria:

  1\) routine blood test: HB≥90g/L(no blood transfusion in 14 days); ANC≥1.5×109/L; White blood cell counts≥3.5×109/L; PLT≥90×109/L; 2) blood biochemical test: ALT and AST ≤2.5×ULN(times the upper limit of normal) and if liver/bone metastases≤5×ULN; TBIL ≤1.5 ULN; Serum Cr≤1.5×ULN and CrCL≥60 ml/min; 3) APTT, INR and PT≤1.5×ULN;
* The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research.

Exclusion Criteria:

* Prior therapy with anti-angiogenic drugs, such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, surufatinib, regorafenib or fruquintinib ect, or with anti-PD-1(L1) or anti-CTLA-4 agents;
* Patients who get other monoclonal antibodies have severe hypersensitivity;
* Present or along with other malignancies within 5 years. Exceptions include cured basal cell carcinoma of the skin or in situ prostate cancer or in situ cervical cancer;
* Patients have any active autoimmune disease that required systemic treatment, including but not limited to autoimmune hepatitis, enteritis, vasculitis, nephritis; asthma that require bronchodilators for medical intervention. Exceptions include patients with vitiligo, psoriasis, alopecia or well-controlled type 1 diabetes but not required systemic treatment, or hypothyroidism with normal thyroid function after alternative treatment;
* In the past, there is a treatment toxicity of CTCAE5.0 ≥2 grade that has not been completely relieved (the adverse reaction grades in this article, unless otherwise specified, are defaulted to the CTCAE 5.0 standard);
* Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (\>10mg/day prednisone or equivalent) or any other form of immunosuppressive therapy, and continued to be used within 2 weeks before the first dose in this study;
* Those with multiple factors affecting oral drugs (such as inability to swallow, post gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
* Imaging (CT or MRI) shows that the tumor has invaded or unclearly separated the large blood vessels;
* Patients with active bleeding, or unexplained persistent decline in hemoglobin should postpone their screening/enrollment until the bleeding stops and the investigator judges it to be safe;
* Within 4 weeks before the first dose in this study, patients with CTCAE5.0 grade 3+ bleeding; patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; on the premise that the international normalized ratio of prothrombin time (INR) ≤1.5, it is allowed to use low-dose warfarin (≤1mg/D), low-dose heparin (≤12000U /D) or low-dose aspirin (≤100mg/D) for preventive purposes;
* Within 4 weeks before the first dose in this study, patients with unhealed wounds, fractures, gastric and duodenal active ulcers, ulcerative colitis, or unresected tumors have active bleeding, or may be caused as determined by the researchers other conditions of gastrointestinal bleeding and perforation, have undergone major surgery (excluding vascular access surgery), inoculated with preventive vaccine or attenuated vaccine;
* Received the treatment of proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions within 2 weeks before the start of the study treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.); or received drugs with immunomodulatory effects (including thymosin, interferon, and interleukin, except for local use to control pleural effusion or ascites);
* History of organ or blood transplantation;
* Patients have active diverticulitis, abdominal abscess, gastrointestinal obstruction;
* Patients with any severe and/or uncontrollable disease, including:

  1\) Patients with unsatisfactory blood pressure control (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg); 2)Within 6 months of the first administration patients with myocardial ischemia or myocardial infarction, arrhythmia that require treatment (including QTC ≥480ms), and grade ≥2 congestive heart failure; 3) active or uncontrolled serious infection (≥CTCAE5.0 Grade 2 infection), tuberculosis patients; 4) Known clinical history of liver disease, including viral hepatitis, carriers of hepatitis b virus must be excluded from active HBV infection, i.e., HBV DNA positive (\>2500 copy /mL or \>500IU/mL);known hepatitis c virus infection (HCV) and HCV RNA positive (\>1 x 10\^3 copy /mL), or other decompensated liver disease, chronic hepatitis requires antiviral treatment; 5) HIV test positive or Syphilis Testing RPR positive; 6) Diabetes is poorly controlled (fasting blood glucose (FBG) ≥10mmol/L); 7) Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantification is more than 1.0 g;
* Those considered by the researcher to be unsuitable for inclusion.