| Eligibility |
Inclusion Criteria:
- 1)Enrollees in this study will be voluntary participants who sign a written informed
consent form and are capable of adhering to scheduled visits and related procedures.2) Ages
between 18 and 75 years old.3) Histologically or cytologically confirmed cases of
persistent, recurrent, or metastatic cervical squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma. Note: A pathological report is necessary for confirmation of the
original primary tumor histology.4) Must have experienced failure with at least one
standard systemic treatment and documented disease progression: Failure is defined as
progression or recurrence within six months after at least one cycle of standard systemic
treatment. Patients who have developed immune acquired resistance may also be included if
they experienced PD after achieving CR or PR with anti-PD-1/PD-L1 antibody treatment, or PD
after experiencing SD=6 months with anti-PD-1/PD-L1 antibody treatment.
5) Not suitable for local treatments such as unresectable surgery and/or definitive
concurrent radiotherapy and chemotherapy.6) The interval between the end of previous
systemic treatment and the first dose of the study drug must be =2 weeks. Additionally, any
treatment-related adverse events must have recovered to a grade =1 according to Common
Terminology Criteria for Adverse Events (CTCAE) V5.0 (excluding hair loss and fatigue).7)
At least one measurable target lesion must be present according to RECIST V1.1
criteria.8)At least one lesion that can receive local injection therapy using recombinant
human adenovirus type 5 should also meet RECIST V1.1 criteria as a measurable lesion.9)
ECOG PS 0 or 1.10) The anticipated survival time should be =12 weeks.11) Female subjects of
reproductive age are required to use effective contraception throughout the treatment
period and for at least 5 months after their final dose of the investigational drug.12)
Participants must consent to providing an adequate amount of tumor tissue samples for PD-L1
expression detection, which may include archived tumor samples such as paraffin blocks or a
sufficient number of unstained slides meeting the study's detection requirements. If no
archived tumor tissue samples are available, participants agree to undergo biopsy of the
tumor lesion.13)With good organ and hematopoietic function.
Exclusion Criteria:
- 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
|
