A Phase Ⅱ/Ⅲ Study of Rulonilimab Plus Chemotherapy± Bevacizumab for the First-Line Treatment of Persistent, Recurrent or Metastatic Cervical Cancer

Inclusion Criteria:

1. Women aged 18 years and above;

2. Patients with advanced ([FIGO] stage IVB) cervical cancer, patients with persistent,recurrent or metastatic cervical cancer that progresses confirmed by histopathologyor cytology, and the following conditions must be met: Programmed Cell Death Ligand 1 (PD-L1) positive expression defined by CombinedPositive Score (CPS) ≥1; The histopathology types include squamous cell carcinoma,adenocarcinoma, or adenosquamous cell carcinoma; Not amenable to curative surgery orconcurrent chemoradiotherapy; No prior systemic therapy for advanced, persistent,recurrent or metastatic disease; Patients who had previously received first-lineplatinum-containing adjuvant or neoadjuvant chemotherapy/radical concurrentchemoradiotherapy and whose time from the last chemotherapy to disease progressionwas > 6 months were eligible for inclusion.

3. According to RECIST1.1 criteria, subjects must have at least one measurable targetlesion examined by Imaging tests (including Not to receive radiation therapy orother locoregional therapy unless the lesion PD or has tumor activity bybiopsy-confirmed);

4. Those with 0-1 scores on the American Eastern Oncology Collaboration Group (ECOG)scale

5. Expected survival ≥3 months;

6. Those who agree to provide archived tumor tissue samples or before randomized within 3 years or fresh tissue samples;

7. The function of vital organs meets the following requirements (drugs with bloodcomponents and cell growth factors are not allowed to be used within 2 weeks beforethe first administration) : Blood routine: Absolute neutrophil count ≥1.5×109/L; Platelet ≥75×109/L; Hemoglobin ≥90g/L; Liver function: TBIL≤1.5×ULN, ALT and AST≤2.5×ULN; If liver metastasis waspresent, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤1.5×ULN a creatinine clearance (CrCl) ≥ 50 mL/min if Cr>1.5×ULN; Coagulationfunction: International Normalized ratio (INR) ≤1.5×ULN and activated partialthromboplastin time (APTT) ≤1.5×ULN. Thyroid function: Thyroid stimulating hormone (TSH) in the normal range; If TSH isabnormal, free triiodothyronine (FT3) and free thyroxine (FT4) must be normal orabnormal without clinical significance.

8. Willingness to participate in the clinical trial; completely understanding andknowing about the study and signing the ICF; willingness and capability to complywith the requirements of the study.

Exclusion Criteria:

1. Patients with pathological tissue types of mucinous adenocarcinoma, gastricadenocarcinoma, clear cell adenocarcinoma, mesonephric tubular adenocarcinoma andother special types of adenocarcinoma；

2. Those who previously treated with T-cell co-stimulation, Antiangiogenic drugs (bevacizumab), immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, oranti-CTLA-4 antibodies), Targeting immune co-stimulatory factors drug (ICOS, CD40,CD137, GITR, OX40 antibodies);

3. Those who have received anti-tumor treatment within 4 weeks before the first dose orwithin 5 half-lives of the drug (whichever is shorter);

4. Immunosuppressive, systemic hormone therapy within 2 weeks prior to initialadministration for immunosuppressive purposes (daily dose equivalent toprednisone>10mg of systemic corticosteroid);

5. The toxicity of previous anti-tumor therapy did not return to CTCAE V5.0 ≤ grade 1 (except hair loss);

6. A history of other malignancies within the last 5 years, except locally curablecancers (limited to Radical melanoma, basal cell or squamous cell skin cancer,superficial bladder cancer, or carcinoma in situ of the breast);

7. Patients with primary central nervous system (CNS) malignancies, CNS metastases thathave failed local treatment, and carcinomatous meningitis; the following conditionscan be included (regular imaging examinations of the disease site): a. Noprogressive CNS symptoms caused by brain metastases, no need for steroid hormonetreatment, and the lesion is less than 1.5 cm; b. Stable for ≥4 weeks after adequatetreatment and neurological symptoms (excluding residual signs or symptoms) havereturned to baseline levels for >2 weeks before the first dose;

8. Patients with uncontrollable pleural effusion, pericardial effusion or peritonealeffusion that requires repeated drainage (more than once a month) (can be enrolledafter stable treatment for more than 1 month);

9. Patients with a history of organ transplantation or allogeneic bone marrowtransplantation; or autologous stem cell transplantation within 3 months before thefirst dose;

10. Patients who have undergone major surgery or have not yet recovered from surgerywithin 4 weeks before the first dose (except for diagnostic surgery);

11. Physical examination or laboratory test findings: Hepatitis B: HBsAg positive and/or HBcAb positive, and HBV-DNA>500IU/mL or 2500copies/mL; Hepatitis C: HCV antibody positive, and HCV-RNA positive or above theupper limit of normal value; Human immunodeficiency virus antibody (Anti-HIV)positive; Active Treponema pallidum infection;

12. Patients with thrombosis who need treatment in the acute stage;

13. Those who have uncontrolled or severe cardiovascular disease, such as New York HeartAssociation (NYHA) Class II or above congestive heart failure or LVEF<50%, unstableangina, myocardial infarction and other cardiovascular disease within 6 monthsbefore the first dose; Poorly controlled arrhythmias; Difficult to controlhypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg after drug therapy);

14. Patients with the following medical histories, including but not limited to activeautoimmune diseases, active infections (such as active tuberculosis), severe mentalillness, severe endocrine diseases (such as type 1 diabetes, type 2 diabetes thatcannot be controlled by drugs), etc.;

15. have been treated with any other investigational drug/device within 4 weeks prior toinitial dosing;

16. Those who have a history of drug abuse or alcoholism within 6 months before thefirst dose;

17. Those with a history of severe allergies, known subjects to have been allergic tomacromolecular protein preparations/monoclonal antibodies and any components of theexperimental drugs;

18. Those who have received live or attenuated live vaccines within 4 weeks before thefirst dose or are scheduled to receive live or attenuated live vaccines during thestudy;

19. Pregnant or lactating women, and female subjects of childbearing age who do notagree to use medically recognized effective contraceptive measures (such asintrauterine devices or condoms) during the study and within 6 months after the lasttrial drug treatment;

20. Those who were judged not suitable for inclusion by the researchers.

21. The following conditions are only applicable to those who are excluded from the useof bevacizumab:

22. Within 3 months before the first dose, there is clinically significanthematuria, hematemesis or hemoptysis (>2.5mL red blood), or other history ofobvious bleeding (such as pulmonary hemorrhage);

23. Patients who are receiving thrombolytic/anticoagulant therapy, or need tocontinue to receive thrombolytic/anticoagulant therapy during the study (prophylactic use of low-dose aspirin is allowed);

24. Patients with unhealed, poorly healed wounds or untreated fractures;

25. Patients with evidence of gastrointestinal perforation, fistula,intra-abdominal abscess, and free gas in the abdominal cavity within 6 monthsbefore the first dose;

26. Subjects with urine protein>1+ undergo 24-hour urine protein quantification,and urine protein ≥1g/24 hours;

27. Patients with reversible posterior encephalopathy syndrome (PRES) or reversibleposterior leukoencephalopathy syndrome (RPLS).