The Combination of Camrelizumab and Apatinib as Second-line Therapy for Advanced Pancreatic Carcinoma

Inclusion Criteria:

1. Subjects voluntarily joined the study and signed informed consent. Able to comply withthe required protocol and follow-up procedures;

2. Histologically or cytologically confirmed recurrent / metastatic advanced pancreaticcancer, have received gemcitabine or nab-paclitaxel based standard chemotherapy;

3. Male and Female, Age ≥ 18 years and ≤ 70 years;

4. Life expectancy exceeds 3 months;

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2;

6. Patients must have measurable disease per RECIST 1.1;

7. Subjects with previous systemic therapy completed more than 2 weeks can beenrolled,and the treatment-related AE should be restored to NCI-CTCAE v5.0 less thangrade 1 (except for grade 2 hair loss)

8. Subjects with asymptomatic central nervous system metastasis, or asymptomatic brainmetastases after treatment, need to be examined by CT or MRI, disease stable for atleast 3 months, and at least 4 weeks without steroid medication;

9. Subjects must provide tumor tissue and blood samples for specific index testing;

10. The HBsAg test is negative; if the HBsAg or HBcAb test is positive, the HBV DNA testmust be less than 1000 IU / ml;

11. The HCV-Ab test is negative; if the HCV-Ab or HCV-RNA test is positive, ALT and ASTCTCAE v5 ≤ 1 level and ≤ 3 × ULN; The joint infection of hepatitis B and C shouled beexcluded;

12. Subjects must have adequate organ function (without blood transfusion, without growthfactor or blood components support within 14 days before enrollment)as determined by:Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 90×109/L ; Total bilirubin ≤ 1×upper limit of normal(ULN)；alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×upper limit of normal(ULN), for subjectswith liver metastases, ALT and AST≤5×ULN; Alkaline phosphatase ≤ 2.5 × upper limit ofnormal(ULN); urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × upper limit ofnormal(ULN);

13. Women of childbearing age should agree to use contraceptives (such as intrauterinedevices, contraceptives or condoms) during the study period and within 6 months of theend of the study; the serum or urine pregnancy test is negative within 7 days prior tostudy enrollment, and Must be non-lactating; males should agree to use contraceptivesduring the study period and within 6 months of the end of the study period.

Exclusion Criteria:

1. There is a third space effusion that cannot be controlled by drainage or other methods (e.g., large amounts of pleural and ascites), and the efficacy of clinical treatmentcannot be evaluated;

2. Subjects who are ready to undergo or have previously undergone organ or bone marrowtransplantation;

3. Subjects with known active CNS metastases or cancerous meningitis；

4. Surgical and/or radiotherapy failed to radically treated spinal cord compression, orpreviously diagnosed spinal cord compression did not have clinical evidence fordisease stable more than 1 week before the first administration；

5. Imaging examination showed that there was a clear manifestation of tumor invading theabdominal great vessels；

6. Subjects with grade II or above myocardial ischemia, myocardial infarction, unstableangina pectoris and uncontrolled arrhythmia within six months before the firstadministration;

7. Subjects with grade III or IV cardiac insufficiency according to the New York HeartAssociation (NYHA) criteria or color Doppler chocardiography showed left ventricularejection fraction (LVEF < 50%) ;

8. Peripheral neuropathy with CTCAE V5 ≥ grade II;

9. Human immunodeficiency virus (HIV) infection;

10. Subjects have active pulmonary tuberculosis;

11. Previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonia,drug-related pneumonia, severe impairment of lung function, etc. may interfere withthe detection and management of suspected drug-related pulmonary toxicity；

12. Subjects had known active or suspected autoimmune disease.Enrollment was allowed to bestable and did not require systemic immunosuppressive therapy；

13. Subjects received the vaccine within 28 days before the first use of the study drug；

14. Subjects requiring systemic corticosteroids (>10 mg/day prednisone or equivalent dosesof the same drug) or other immunosuppressive therapy within 14 days before or duringthe first dose of the study drug.Enrollment was allowed if inhaled or topical steroidsor adrenaline replacement therapy at a dose of <10 mg/day prednisone were allowed inthe absence of active autoimmune disease；

15. Any active infection requiring systemic anti-infective treatment occurred within 14days prior to the first administration of the study drug；

16. Radiotherapy, chemotherapy, surgical treatment or other targeted therapy forpancreatic cancer had been received within 1 week before the first administration ofthe study drug and had not progressed from previous treatment;

17. Major surgery was performed within 28 days before the first administration. Thedefinition of major surgery in this study is that recovery time of at least 3 weeksafter surgery is required to be able to accept the surgery treated in this study.Tumoraspiration or lymph node biopsy allowed enrollment；

18. Subjects received radical radiotherapy within 3 months before the first administrationof the study drug;

19. Other anti tumor treatments may be received during the study interval.Such aschemotherapy or radiotherapy (except palliative radiotherapy);

20. Subjects have previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 oranti-CTLA-4 antibody treatment, or any other antibody or T cell co-stimulation drugsor any drugs that target immune checkpoint;

21. Participating in other clinical studies or planning to start this study is less than 14 days from the end of treatment in a previous clinical study;

22. Severe allergy to any monoclonal antibody or study drug excipient;

23. Women who are pregnant or breastfeeding, those with fertility who are unwilling orunable to take effective contraception;

24. Known history of psychotropic drug abuse or drug use. Subjects who have stoppeddrinking can be enrolled；

25. The investigator judged that the subjects had other factors that could lead to theforced termination of the study.