Fruquintinib Plus PD-1 Antibody in pMMR / MSS Locally Advanced Rectal Cancer (LARC) With High Immune Score

Inclusion Criteria:

1. 18-75 yrs old;
2. pMMR/MSS rectal adenocarcinoma;
3. Pelvic MRI / endoscopic ultrasonography or transrectal ultrasound were used forreoperative staging: T3-4N+ with resectable tumor;
4. High immune score (Immunoscore®️ ≥3);
5. No sign of bowel obstruction, or bowel obstruction has been relieved by ostomy;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
7. No previous chemotherapy, radiotherapy or immunotherapy;
8. Distant metastasis was excluded by CT of chest, abdomen and pelvis before operation;
9. Able to swallow tablets;
10. Life expectancy of at least 2 years;
11. Adequate organ function;
12. Female participants of childbearing potential must be willing to use adequatecontraception for the course of the study starting with the first dose of studymedication through 120 days after the last PD-1 antibody dose; Male participants mustagree to use adequate contraception for the course of the study starting with thefirst dose of study medication through 120 days after the last PD-1 antibody dose.

Exclusion Criteria:

1. Any active autoimmune disease or history of autoimmune disease;
2. Immunosuppressants, systemic or absorbable local hormones are being used to achievethe purpose of immunosuppression (dose > 10mg / day, prednisone or other effectivehormones) and continue to be used within 2 weeks before enrollment;
3. History of severe allergic reaction to monoclonal antibody;
4. Subjects with untreated active brain metastasis or meningeal metastasis with clinicalsymptoms;
5. Suffering from hypertension and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg);
6. Have previously received other PD-1 antibody therapy or other immunotherapy againstPD-1 / PD-L1, or have previously received anti angiogenesis drugs;
7. There are cardiac clinical symptoms or diseases that are not well controlled, such as: (1) heart failure above NYHA grade 2 (2) unstable angina pectoris (3) myocardialinfarction within 1 year (4) clinically significant supraventricular or ventriculararrhythmias requiring treatment or intervention;
8. Known hereditary or acquired bleeding and thrombotic tendency (such as hemophilia,coagulation dysfunction, thrombocytopenia, hypersplenism, etc.) or undergoingthrombolytic or anticoagulant therapy;
9. Urine routine examination indicates that urinary protein is ≥ + +, or confirmed 24-hour urinary protein is ≥ 1.0g;
10. Significant clinical bleeding symptoms or definite bleeding tendency occurred within 3months before enrollment, such as gastrointestinal bleeding, active bleeding, baselinefecal occult blood + + or above, or vasculitis;
11. Arteriovenous thrombosis events occurred within 6 months before enrollment, such ascerebrovascular accidents (including transient ischemic attack, intracerebralhemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism;
12. Subjects with active infection;
13. Congenital or acquired immune deficiency (such as HIV infection) or active hepatitis (hepatitis B: HBsAg positive and HBV DNA > 104 copy number /ml; Hepatitis C: HCVantibody positive);
14. Those who participated in clinical trials of other drugs within 3 months beforeenrollment;
15. There was evidence of distant metastasis before operation;
16. History of pelvic or abdominal radiotherapy;
17. Any other malignant disease within the preceding 5 years with the exception of curedskin basal cell carcinoma, cervical carcinoma in situ and ovarian cancer;
18. Live vaccines were administered less than 4 weeks before the study or possibly duringthe study period;
19. Known or suspected allergy to the study drug or to any drug given in connection withthis test;
20. In the judgment of the researcher, the subject has other circumstances that may affectthe results of the study or cause the study to be forced to stop halfway.