Effect of Compound Kushen Injection Combined With Pabolizumab in the Treatment of Cervical Adenocarcinoma

Inclusion Criteria:

1. Female, aged ≥ 18 yrs and ≤75 yrs;
2. Patients volunteered to participate in this study, signed informed consent, goodcompliance, and cooperated with follow-up;
3. The subjects' damage caused by other treatments has been recovered (NCI CTCAE version 5.0 grade ≤ grade 1), ECOG score ≤ 2 points;
4. Expected survival is longer than 3 months;
5. Pathological diagnosis of cervical advanced adenocarcinoma (PD-L1 positive, TPS score ≥1%; CPS score ≥1);
6. Evaluable lesions: CT scan of tumor lesions ≥5mm in length, CT scan of lymph nodelesions ≥10mm in length, and scan layer thickness not greater than 5mm (refer toRECIST 1.1);
7. The first diagnosis was confirmed by pathology and / or cytology to be metastatic, orrecurrent, persistent cervical adenocarcinoma (mainly refers to tumors remaining orprogressing at least 3 months after initial radiotherapy or concurrentchemoradiotherapy), and the patient can no longer accept Surgery or chemoradiation;
8. Subject agrees to take blood sample;
9. Subjects can provide formalin-fixed, paraffin-embedded tumor tissue samples forsubsequent related testing (optional);
10. A.Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.0×109/L ; platelets >=100×109/L B. Biochemical test standards: a. Alanineaminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 times the upper limitof normal value (ULN). If with liver metastases, ALT and AST ≤ 5 × ULN; b. Totalbilirubin (TBIL) ≤ 1.5 × ULN; c. Serum creatinine (Cr) ≤ 1.5 × ULN or creatinineclearance (CCr) ≥ 60ml / min; d. Doppler ultrasound evaluation: left ventricularejection Blood fraction (LVEF) ≥ the lower limit of normal value (50%).
11. Women of childbearing age should agree that contraception (such as an intrauterinedevice, contraceptive, or condom) must be used during the study and within 3 monthsafter the last dose; a serum or urine pregnancy test must be negative within 14 daysof study enrollment and must be Non-lactating patients. Sign written informed consentbefore conducting any research-related procedures.

Exclusion Criteria:

1. People who are known to be allergic to compound kushen injection and pabolizumab or toactive or inactive ingredients of drugs with similar chemical structures to compoundkushen injection and pabolizumab.
2. Symptomatic, uncontrolled brain metastases or pia meningeal metastases.
3. No imaging scan is required to confirm brain-free metastases; patients with spinalcord compression may still be considered if they have received targeted treatment andhave evidence of clinical stability of the disease for at least> 28 days (controlledcentral nervous system metastasis must be in the study Have received treatment such asradiation or chemotherapy for at least 1 month; patients must not have new symptomsrelated to central nervous system lesions or symptoms that indicate diseaseprogression, and patients either take a stable dose of hormones or do not need to takehormones).
4. Underwent major surgery within 3 weeks before the study began, or any surgical effectsthat have not recovered after surgery, or received chemotherapy.
5. Received> 20% bone marrow palliative radiotherapy 1 week before enrollment.
6. Have aggressive cancers other than cervical cancer (except fully treated basal orsquamous cell skin cancer within 2 years before enrollment).
7. Patient has a previous or current diagnosis of myelodysplastic syndrome (MDS) or acutemyeloid leukemia (AML).
8. Suffering from a serious or uncontrolled illness, including but not limited to:
9. Uncontrollable nausea and vomiting, inability to swallow research drugs, and anygastrointestinal disorders that may interfere with the metabolism of the drug.
10. Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C,etc.
11. Uncontrolled major seizures, unstable spinal cord compression, superior vena cavasyndrome, or other mental illnesses that prevent patients from signing informed consent.
12. Immunodeficiency (except splenectomy), or other diseases that the investigator believesmay expose patients to high-risk toxicity.
13. History of bleeding and thrombosis:
14. Any CTCAE Grade 2 bleeding event within 3 months prior to screening, or CTCAE Grade 3and above bleeding events within 6 months prior to screening.
15. History of gastrointestinal bleeding or clear gastrointestinal bleeding tendencywithin 6 months before screening. Such as: esophageal varices at risk of bleeding,focal lesions of locally active ulcers, or fecal occult blood +.
16. Have active bleeding or coagulopathy, have a tendency to bleed, or are receivingthrombolytic or anticoagulant therapy.
17. Patients need anticoagulation with drugs such as warfarin or heparin.
18. Patients need long-term antiplatelet therapy (eg aspirin, clopidogrel).
19. Thrombosis or embolism events in the past 6 months, such as: cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism.
20. Serious cardiovascular history:
21. NYHA (New York Heart Association) Grade 3 and 4 congestive heart failure.
22. Suffering from unstable angina or newly diagnosed angina or myocardial infarctionwithin 12 months before screening.
23. Arrhythmias requiring therapeutic intervention (patients taking beta-blockers ordigoxin can be enrolled).
24. CTCAE≥ grade 2 valvular heart disease.
25. Poorly controlled hypertension (systolic blood pressure> 150 mmHg or diastolic bloodpressure> 100 mmHg).
26. Other laboratory inspection abnormalities:
27. Hyponatremia (sodium <130 mmol / L); baseline serum potassium <3.5 mmol / L (beforeentering the study, potassium supplements can be used to restore serum potassium abovethis level).
28. Abnormal thyroid function, and drugs cannot maintain thyroid function within normalrange.
29. Any previous or current disease, treatment, or laboratory abnormality that mayinterfere with the results of the study, affect the patient's full participation in thestudy, or the investigator believes that the patient is not suitable to participate in thestudy; the patient may not receive platelets within 4 weeks before the study drug beginsRed blood cell infusion.
30. Patients who are pregnant or breastfeeding, or plan to become pregnant during studytreatment.
31. Corrected QTc interval (QTc)> 450 milliseconds; if the patient has a prolonged QTcinterval, but the investigator evaluates that the reason for the prolongation is apacemaker (and no other cardiac abnormalities), it is necessary to discuss with theinvestigator to determine whether the patient is suitable Group study.
32. With any active autoimmune disease or have a history of autoimmune disease (includingbut not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis,hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism;patients with vitiligo or asthma has been completely relieved in childhood and do not needany intervention after adulthood could be included; Asthma patient who need bronchodilatorsfor medical intervention cannot be included) 17. Treatment with other immunosuppressivemedications, systemic or topical corticosteroids (>10 mg daily prednisone or equivalent)within 14 days before enrollment.
33. With a history of severe allergic reaction to other monoclonal antibodies. 19. Evidenceof central nervous system metastasis (such as brain edema requiring hormone intervention,or brain metastasis progression). Patients who have previously received treatment for brainor meningeal metastasis and persistently stable (MRI) for at least 1 month thus stoppedsystemic hormone therapy (dose > 10mg/ prednisone or other therapeutic hormones) for morethan 2 weeks can be included.
34. Have previously received any PD-1/PD-L1 inhibitor treatment.