A Clinical Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsules Versus Paclitaxel as Weekly Treatment of Relapsed Platinum-resistant Ovarian Cancer

Inclusion Criteria:

• 1. The subjects voluntarily joined the study, signed the informed consent form(ICF),and had good compliance;
• 2. age: 18-75 years old (when signing ICF; Eastern Cooperative Oncology Group (ECOG)Performance Status(PS) score 0-1; estimated survival time is more than 3 months;
• 3. Epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancerconfirmed by histopathology or cytopathology;
• 4. Subjects had disease recurrence or progression during prior chemotherapy withplatinum-based regimens or within 6 months after the last dose of chemotherapy withplatinum-based regimens (for at least 4 courses of treatment). Note: The definition ofdisease recurrence or progression needs to meet either of the following two items:a.Evidence of objective radiographic or clinical disease progression (for example,cytological reports of new ascites or pleural effusion); b.Persistent elevation oftumor marker CA125 (confirmed 1 week later) accompanied by clinical symptoms orphysical examination indicating disease progression.
• 5. The number of previous chemotherapy regimens does not exceed 4 lines, and it isrequired that no more than 1 systemic treatment regimen is accepted after platinumresistance;
• 6. At least one measurable lesion was confirmed according toResponse EvaluationCriteria in Solid Tumors 1.1( RECIST 1.1) criteria;
• 7. The function of main organs are well and meet the following standards: (1) RoutineBlood routine examination standards (without blood transfusion or correction withhematopoietic stimulating factor drugs within 7 days before the examination ): a)Hemoglobin（HGB） ≥90 g/L; b) Absolute value of neutrophil（NEUT）≥1.5×109/L; c) Plateletscount（PLT）≥ 80×109/L. (2) The biochemical examination shall meet the followingstandards: a) Total bilirubin (TBIL) ≤ 2 times the upper limit of normal (ULN) (Patients with Gilbert syndrome ≤ 3 × ULN); b) Alanine aminotransferase (ALT) andaspartate aminotransferase (AST)≤2.5×ULN. If it is accompanied by liver metastasis,ALT and AST≤5×ULN; c) Serum creatinine (CR) ≤ 1.5×ULN or Creatinine clearance (CCR) ≥60ml/min (Cockcroft-Gault glomerular filtration formula). d）Serum albumin (ALB) ≥30g/L (no albumin supplement within 7 days). (3) Blood coagulation function orthyroid function test should meet the following standards: a) Prothrombin time (PT), activated partial thromboplastin time (APTT), internationalnormalized ratio (INR)≤1.5×ULN (no anticoagulant therapy); b) Thyroid StimulatingHormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be examined. If T3 and T4levels are normal, it can be selected. (4) Heart color Doppler ultrasound assessment:Left ventricular ejection fraction (LVEF) ≥50%. (5) Urine routine: urine protein <2+ (when the baseline urine protein ≥ 2+, thepatient will undergo a 24-hour urine protein quantitative test within 7 days, and canonly be selected when urine protein <1g);
• 8. Women must meet one of the following conditions:

1. Surgical sterilization has been performed;
2. For those who have been menopausal, the menopause has been stopped for at least 1year; (3) Women with fertility must meet the following conditions: The serumpregnancy test before the first administration is negative and must benon-lactating subjects;During the entire study period, agree to use an approvedmethod of contraception (for example: oral contraception, injection contraceptionor implanted, barrier contraception, spermicides and condoms, Intrauterinedevices), and the method of contraception remained unchanged throughout the studyperiod.

Exclusion Criteria:

• 1. Other malign combined diseases and medical history:

1. Suffering from other non-epithelial ovarian tumors (for example, germ celltumors, sex cord stromal tumors) or borderline ovarian epithelial tumors;
2. Other malignant tumors appeared or were present within 3 years. The following twocases can be included: other malignant tumors treated by single operation haveachieved 5-year DFS in a row; The cured cervical carcinoma in situ, non melanomaskin cancer and superficial bladder tumor [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];
3. There are Multiple factors affecting oral medications (such as inability toswallow, chronic diarrhea and intestinal obstruction, etc.);
4. Unrelieved toxic reactions higher than CTCAE level 1 caused by any previoustreatment, excluding hair loss;
5. Received major surgical treatment, open biopsy, or suffered obvious traumaticinjury within 28 days before the start of the study treatment;
6. Long-term unhealed wounds or fractures;
7. Arterial/venous thrombosis events occurred within 6 months, such ascerebrovascular accident (including transient ischemic attack, cerebralhemorrhage and cerebral infarction), deep vein thrombosis and pulmonary embolism,etc; (Prophylactic use of anticoagulant therapy is allowed for patients withthrombotic tendency or undergoing anticoagulant therapy.)
8. Those who have a history of psychotropic drug abuse and cannot be quit or havemental disorders; i) Subjects with any severe and/or uncontrolled disease,including:
9. After more than two kinds of drug treatment, blood pressure control is stillnot ideal (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg);
10. Patients with grade ≥ 2 myocardial ischemia or myocardial infarction,arrhythmia (including corrected QT interval (QTc) ≥ 450ms (male) and QTc ≥ 470ms (female) and grade ≥ 2 congestive heart failure (New York HeartAssociation (NYHA) classification);
11. Active or uncontrolled severe infection (≥ CTCAE grade 2 infection);
12. Abnormal liver*:

• Hepatitis B virus infection, HBsAg positive, HBV DNA positive or copynumber exceeds the upper limit of normal value in the research center;Remarks: Continuous antiviral therapy (nucleoside analogues arerecommended) and monitoring of HBV DNA every 3 to 6 months arerecommended for HBsAg positive patients eligible for inclusion，HBcAbpositive subjects but _HBsAg negative subjects can be monitored for HBVDNA every 3 to 6 months, and antiviral therapy is required if the virusis activated.
• Hepatitis C virus infection, HCV antibody positive, HCV RNA positive orthe test value exceeds the upper limit of the normal value of theresearch center; Remarks: Patients with HCV who are eligible forinclusion also need continuous antiviral therapy to prevent viralactivation and can be monitored for HCV RNA every 3-6 months. If thevirus is activated, direct antiviral therapy without interferon isrecommended.

5. Patients with renal failure requiring hemodialysis or peritoneal dialysis;
6. Patients with a history of immunodeficiency, including HumanImmunodeficiency Virus (HIV) positive or other acquired or congenitalimmunodeficiency disease, or with a history of organ transplantation;
7. Previous or existing interstitial pneumonia, (non-infectious) pneumonia thatrequires adrenal corticosteroid therapy, currently suffering from othertypes of pneumonia ≥ 2, or lung function tests confirmed severely impairedlung function (Forced Expiratory Volume in the first second (FEV1) ordiffusing capacity of lung for carbon monoxide ( DLCO) or DLCO per alveolarvolume (DLCO /VA) accounts for the expected value %<40%) and other objectiveevidence;
8. Poor control of diabetes (Fasting Blood Glucose (FBG) > 10mmol/L);
9. Patients suffering from epilepsy and requiring medical treatment;

• 2. Tumor-related symptoms and treatment:

1. Patients who had received surgery, chemotherapy, radiotherapy, hormone therapy,biotherapy, and immunotherapy within 4 weeks before the start of the studytreatment (the washout period was calculated from the end of the last treatment);Patients who had previously received local radiotherapy could be included if theymet the following conditions: The end of radiotherapy was more than 4 weeks afterthe start of study therapy (brain radiotherapy was more than 2 weeks); And thetarget lesions selected in this study are not in the radiotherapy area; Or thetarget lesion is located in the radiotherapy area, but progression is confirmed.
2. Received the treatment of proprietary Chinese medicines with anti-tumorindications specified in the National Medical Products Administration (NMPA)approved drug instructions within 2 weeks before the start of the study treatment (Including compound cantharidin capsules, Kangai injection, Kanglaitecapsule/injection, Aidi injection, brucea javanica oil injection/capsule,Xiaoaiping tablet/injection, Huachansu capsule, etc.);
3. Previously received related immunotherapy drugs for programmed death-1 (PD-1),programmed death-Ligand 1 (PD-L1), cytolytic T lymphocyte-associated antigen-4 (CTLA-4) or similar Tyrosine Kinase Inhibitor (TKI) small moleculeanti-angiogenesis drugs such as Androtinib Hydrochloride;
4. Imaging (CT or MRI) shows that the tumor has invaded the periphery of importantblood vessels or the investigator judges that the tumor is highly likely toinvade important blood vessels and cause fatal massive bleeding during thesubsequent study;
5. Patients with clinical symptoms of pleural effusion, pericardial effusion orascites requiring Repeated puncture or drainage or those who have receiveddrainage for the purpose of treatment within 1 month before randomization;
6. Subjects with known Central Nervous System (CNS) metastasis and/or cancerousmeningitis; Unless asymptomatic, or treated and stable, no radiographic evidenceof new or enlarged brain metastases was found for at least 4 weeks after brainmetastases treatment, and steroid or anticonvulsant therapy was discontinued forat least 14 days before study treatment began.

• 3. Study treatment related:

1. Live attenuated vaccine vaccination history within 28 days before the start ofthe study treatment or planned live attenuated vaccination during the studyperiod;
2. Patients with a history of severe allergic disease and severe drug allergy.It isknown to be allergic to any component prescribed in paclitaxel or TQB2450injection or Anlotinib hydrochloride capsules prescription;
3. Active autoimmune disease that requires systemic treatment (such as the use ofdisease-relieving drugs, corticosteroid or immunosuppressant) occurred within 2years before the start of the study treatment. Replacement therapy (such asthyroxine, insulin, or physiological corticosteroid for adrenal or pituitaryinsufficiency, etc.) is not considered systemic therapy;
4. Patients who have been diagnosed with immunodeficiency or are receiving systemicglucocorticoid therapy or any other form of immunosuppressive therapy (Dose>10mg/day prednisone or other curative hormones) and are still continuing touse them within 2 weeks of first administration; 4) Participated in otheranti-tumor drug clinical trials within 4 weeks before grouping; 5) According tothe investigator's judgment, subjects who have concomitant diseases thatseriously endanger the safety of the subjects or affect the completion of thestudy, or who are considered unsuitable for inclusion in the group for otherreasons.