Efficacy and Safety of AK104 Combined With Chemotherapy and Recombinant Human Adenovirus 5 Injection in Cervical Cancer

Who cannot join

• 1) Diagnosed with other malignancies within the 5 years preceding initial dosing, excluding surgically cured basal cell carcinoma or squamous cell carcinoma of the skin, in situ carcinoma that has been surgically resected, and/or papillary thyroid carcinoma. Subjects with histologically confirmed small cell (neuroendocrine) cervical cancer, cervical sarcoma, and gastric-type cervical adenocarcinoma.2) Infection at the injection site.3) Presence of ascites, pleural effusion, or pericardial effusion accompanied by clinical symptoms or necessitating drainage. Subjects without clinical symptoms or requiring drainage who have ceased drainage for a minimum of 3 days and show no significant increase in fluid accumulation may be included.4) Individuals scheduled for or having undergone organ or bone marrow transplantation previously.5) Acute or chronic active hepatitis B or C infection with HBV DNA >200IU/ml or 103 copies/ml; positive anti-HCV antibody and HCV-RNA level above detection limit. Those treated with nucleoside analog antiviral agents resulting in HBV DNA/HCV-RNA levels below specified standards can be included.
• 6) Central nervous system (CNS) metastasis involving meningeal metastasis or symptomatic CNS metastasis. Asymptomatic brain metastases patients showing stable symptoms after treatment for at least 2 weeks may participate if they meet specific criteria: measurable lesions outside the CNS; absence of meningeal/midbrain/pons/cerebellum/medulla oblongata/spinal cord metastases; no history of intracranial hemorrhage; cessation of hormone therapy 14 days before first dose.7）Any life-threatening bleeding event within the past three months including need for blood transfusion，surgery，local treatment，or ongoing medication therapy.8）Arterial thrombosis，embolism，or ischemia within six months prior to enrollment including myocardial infarction，unstable angina pectoris ，cerebrovascular accident etc。A history of deep vein thrombosis（DVT）or any other serious thromboembolic events within three months prior to enrollment are not considered "serious" thromboembolic events.9）Hepatic vein thrombosis involving both hepatic portal trunk \& left/right branches；hepatic portal trunk \& mesenteric superior/inferior veins；superior vena cava thrombosis/superior vena cava syndrome.10）Tumor invasion into important surrounding organs/blood vessels such as great mediastinal vessels/superior vena cava/inferior vena cava/abdominal aorta/iliac vessels/trachea/esophagus；risk of tracheoesophageal fistula /mediastinal pleural fistula development.11）Uncontrollable hypertension defined as systolic blood pressure ≥150mmHg/diastolic blood pressure ≥100mmHg/history hypertension crisis/hypertensive encephalopathy.12）Symptomatic congestive heart failure(NYHA class II-IV)/symptomatic/poorly controlled arrhythmias/prolonged QT interval(QTcF>470ms).13）Severe bleeding tendency/coagulation dysfunction/currently receiving thrombolytic therapy.14）History gastrointestinal perforation/fistula last six months/bowel obstruction(including incomplete bowel obstruction requiring parenteral nutrition)/inflammatory bowel disease/extensive bowel resection(Crohn's disease/ulcerative colitis/chronic diarrhea).15 ) History interstitial pneumonitis/drug-induced pneumonitis/radiation pneumonitis/idopathic pneumonitis /active pneumonitis.16 ) Active tuberculosis(TB)，currently receiving anti-TB therapy/or received study drug previous year.17 ) Human immunodeficiency virus(HIV)(HIV1/HIV2 antibody positive), known active syphilis infection.18 ) Active/severely uncontrolled infections hospitalization severe infections(infections/sepsis/severe pneumonia complications etc.)within four weeks prior to first dose.19 ) Oral/intravenous therapeutic antibiotics one week before starting study treatment.20 ) Systemic autoimmune diseases/requiring systemic treatment/two-year history(white vitiligo、psoriasis、alopecia、Graves' disease not requiring systemic treatment/hypothyroidism only needing thyroid hormone replacement/type1 diabetes only needing insulin replacement). Known primary immunodeficiency history Only patients with positive autoimmune antibodies need confirmation by investigator presence autoimmune disease.21 ) Immunosuppressive drugs use four weeks except nasal inhalant local corticosteroids/systemic corticosteroids physiological doses(no more than prednisone equivalent daily doses other cortico steroids temporary use relief breathing difficulties due asthma/COPD).22 ) Live attenuated vaccine four weeks planned during study period.23 ) System immune stimulant treatments four weeks.24)Major surgery(craniotomy/thoracotomy/laparotomy)prior four weeks/unhealed wound ulcer fracture.25)Uncontrolled/metabolic disorder/non-malignant organ/systemic diseases/cancer-related complications/higher medical risk uncertainty survival period evaluation.26) Other acute chronic conditions psychiatric disorders laboratory test abnormalities increasing risk participating study/receiving study drug interfering interpretation results determined investigator patient eligible participate thisstudy.27) Received oncolytic virus therapy past received anti-CTLA-4 antibodytherapy past.28) Known allergic AK104,pemetrexed,cisplatin,and Recombinant Human Adenovirus 5 Injection components/severe allergic reaction monoclonal antibodies past.29) Received investigational drug treatment previousfourweeks starting studytreatment.30) No anticancer therapies received previousfourweeks startingstudyoral chemotherapy(two-week washout oral fluoropyrimidine-based drugs), endocrine targeted therapies(small molecule targeted therapies two-week half-life longer),immunotherapy,tumor embolization Chinese herbal medicine indications.31) Pregnant breastfeeding femalepatients