Niraparib Combined With Brivanib or Toripalimab in Patients With Cervical Cancer

Inclusion Criteria:

1. Female, aged ≥ 18 yrs and ≤70 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 squamous cell carcinoma, adenocarcinoma, andadenosquamous carcinoma;
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 cancer (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 gene 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 zl-2306 (niraparib)，brivanib and toripalimabor to active or inactive ingredients of drugs with similar chemical structures tozl-2306 (niraparib），brivanib and toripalimab. 2.Multiple factors affecting oral medication (such as inability to swallow,post-gastrointestinal resection, chronic diarrhea, etc.). 3.Symptomatic, uncontrolled brain metastases or pia meningeal metastases. No imagingscan is required to confirm brain-free metastases; patients with spinal cordcompression may still be considered if they have received targeted treatment and haveevidence 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). 5.Underwent major surgery within 3 weeks before the study began, or any surgicaleffects that have not recovered after surgery, or received chemotherapy. 6.Received> 20% bone marrow palliative radiotherapy 1 week before enrollment. 7.Haveaggressive cancers other than cervical cancer (except fully treated basal or squamouscell skin cancer within 2 years before enrollment). 8.Patient has a previous or current diagnosis of myelodysplastic syndrome (MDS) oracute myeloid leukemia (AML). 9.Suffering from a serious or uncontrolled illness, including but not limited to:

1. Uncontrollable nausea and vomiting, inability to swallow research drugs, and anygastrointestinal disorders that may interfere with the metabolism of the drug.
2. Active viral infections such as human immunodeficiency virus, hepatitis B,hepatitis C, etc.
3. Uncontrolled major seizures, unstable spinal cord compression, superior vena cavasyndrome, or other mental illnesses that prevent patients from signing informedconsent.
4. Immunodeficiency (except splenectomy), or other diseases that the investigatorbelieves may expose patients to high-risk toxicity. 10.History of bleeding and thrombosis:
5. Any CTCAE Grade 2 bleeding event within 3 months prior to screening, or CTCAEGrade 3 and above bleeding events within 6 months prior to screening.
6. History of gastrointestinal bleeding or clear gastrointestinal bleeding tendencywithin 6 months before screening. Such as: esophageal varices at risk ofbleeding, focal lesions of locally active ulcers, or fecal occult blood +.
7. Have active bleeding or coagulopathy, have a tendency to bleed, or are receivingthrombolytic or anticoagulant therapy.
8. Patients need anticoagulation with drugs such as warfarin or heparin.
9. Patients need long-term antiplatelet therapy (eg aspirin, clopidogrel).
10. Thrombosis or embolism events in the past 6 months, such as: cerebrovascularaccidents (including transient ischemic attacks), pulmonary embolism. 11.Serious cardiovascular history:
11. NYHA (New York Heart Association) Grade 3 and 4 congestive heart failure.
12. Suffering from unstable angina or newly diagnosed angina or myocardial infarctionwithin 12 months before screening.
13. Arrhythmias requiring therapeutic intervention (patients taking beta-blockers ordigoxin can be enrolled).
14. CTCAE≥ grade 2 valvular heart disease. 12.Poorly controlled hypertension (systolic blood pressure> 150 mmHg or diastolicblood pressure> 100 mmHg). 13.Other laboratory inspection abnormalities:
15. Hyponatremia (sodium <130 mmol / L); baseline serum potassium <3.5 mmol / L (before entering the study, potassium supplements can be used to restore serumpotassium above this level).
16. Abnormal thyroid function, and drugs cannot maintain thyroid function withinnormal range. 14.Any previous or current disease, treatment, or laboratory abnormality that mayinterfere with the results of the study, affect the patient's full participationin the study, or the investigator believes that the patient is not suitable toparticipate in the study; the patient may not receive platelets within 4 weeksbefore the study drug begins Red blood cell infusion. 15.Patients who are pregnant or breastfeeding, or plan to become pregnant duringstudy treatment. 16.Corrected QTc interval (QTc)> 450 milliseconds; if the patient has a prolongedQTc interval, but the investigator evaluates that the reason for the prolongationis a pacemaker (and no other cardiac abnormalities), it is necessary to discusswith the investigator to determine whether the patient is suitable Group study. 17.With any active autoimmune disease or have a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia,uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, hypothyroidism; patients with vitiligo or asthma has beencompletely relieved in childhood and do not need any intervention after adulthoodcould be included; Asthma patient who need bronchodilators for medicalintervention cannot be included) 18.Treatment with other immunosuppressivemedications, systemic or topical corticosteroids (>10 mg daily prednisone orequivalent) within 14 days before enrollment. 19.With a history of severe allergic reaction to other monoclonal antibodies 20.Evidence of central nervous system metastasis (such as brain edema requiringhormone intervention, or brain metastasis progression). Patients who havepreviously received treatment for brain or meningeal metastasis and persistentlystable (MRI) for at least 1 month thus stopped systemic hormone therapy (dose > 10mg/ prednisone or other therapeutic hormones) for more than 2 weeks can beincluded. 21.Have previously received any PARP inhibitor or PD-1/PD-L1 inhibitor treatment.