Neoadjuvant Ivonescimab Plus Chemotherapy Followed by Concurrent Chemoradiotherapy in High-Risk Locally Advanced Cervical Cancer

Inclusion Criteria:

* Able to understand and voluntarily sign the written informed consent form before any study-specific procedures.
* Female participants aged ≥18 years on the day of signing informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Expected survival time ≥3 months.
* Histologically confirmed diagnosis of cervical cancer.
* Histological types limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
* No prior anti-tumor treatments (including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy). Note: Lymph node dissection or biopsy for clinical staging is allowed.
* FIGO 2018 stage III-IVA cervical cancer unsuitable for curative surgery. Lymph node metastasis may be confirmed by biopsy or imaging. Imaging-based lymph node metastasis must meet: MRI/CT showing positive lymph node with short-axis diameter ≥10 mm, and ≥15 mm to be used as target lesion.
* At least one measurable lesion per RECIST v1.1 criteria.
* PD-L1 CPS score ≥1 in tumor tissue.
* Must provide tumor tissue sample before treatment (FFPE blocks or ≥5 unstained slides, preferably freshly obtained).
* Adequate organ function as per screening labs:
* Hematological (without transfusion or growth factors within 2 weeks):
* ANC ≥1.5×10⁹/L
* Platelets ≥90×10⁹/L
* Hemoglobin ≥9.0 g/dL
* Renal:
* Creatinine ≤1.5×ULN or CrCl ≥50 mL/min (≥60 mL/min if cisplatin is planned), calculated by Cockcroft-Gault:

CrCl (mL/min) = \[(140 - age) × weight (kg) × 0.85\] / \[serum creatinine (mg/dL) × 72\]

* Hepatic:
* Total bilirubin ≤1.5×ULN (≤3×ULN if Gilbert's syndrome suspected)
* AST and ALT ≤2.5×ULN
* Coagulation:
* INR ≤1.5×ULN and APTT ≤1.5×ULN (unless on anticoagulants with stable dosing)
* Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose, and agree to use effective contraception during treatment and for at least 120 days after last dose of study drug and 180 days after chemoradiotherapy.
* Effective contraception includes hormonal contraception, IUDs, or double barrier methods. Periodic abstinence and rhythm methods are not acceptable.

Exclusion Criteria:

* Cervical cancer of non-eligible histology (e.g., neuroendocrine carcinoma, sarcoma).
* Evidence of distant metastasis, including inguinal lymph node metastasis or lymph node involvement above L1 vertebral level.
* History of total hysterectomy (removal of uterus and cervix). Subtotal hysterectomy or cornuostomy preserving the cervix is acceptable.
* Anatomical or geometric contraindications to brachytherapy.
* Active malignancies within 2 years, except for treated non-melanoma skin cancer, superficial bladder cancer, in-situ breast cancer (note: cervical carcinoma in situ history is exclusionary).
* Bilateral hydronephrosis deemed non-relievable by nephrostomy or ureteral stenting.
* Anti-tumor therapy within 2 weeks before treatment initiation (including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, immunotherapy, or immuno-co-stimulatory agents like ICOS, CD40, CD137, GITR, OX40 antibodies).
* Immunomodulatory drugs (e.g., thymosin, interferon, IL-2) within 2 weeks before treatment.
* Systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressants within 2 weeks, except:
* Inhaled, ophthalmic, or topical steroids ≤10 mg/day prednisone or equivalent
* Physiologic hormone replacement ≤10 mg/day prednisone or equivalent
* Prophylactic corticosteroids for hypersensitivity (e.g., CT contrast)
* Active infections requiring systemic treatment (e.g., active TB, syphilis, systemic fungal infections), except HBV antiviral therapy.
* Severe infection within 4 weeks prior to treatment (e.g., hospitalization, sepsis, severe pneumonia).
* Major surgery or significant trauma (e.g., fractures) within 4 weeks, or planned elective major surgery. Pelvic/para-aortic lymph node dissection not exclusionary.
* Live vaccines within 4 weeks.
* Active or history of autoimmune diseases except for:
* Vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy
* Autoimmune thyroiditis requiring only stable hormone therapy
* Type I diabetes requiring only stable insulin replacement
* Any of the following cardiovascular/cerebrovascular diseases:
* MI, unstable angina, PE, aortic dissection, DVT, or arterial embolism within 6 months
* NYHA Class II or greater heart failure
* Significant arrhythmias needing long-term treatment (stable asymptomatic Afib allowed)
* Stroke (CVA) within 6 months
* LVEF \<50%
* History of myocarditis or cardiomyopathy
* Known primary or secondary immunodeficiency, including HIV antibody positivity.
* Active HBV infection: HBsAg positive with HBV DNA \>1000 IU/mL or \>5000 copies/mL; active HCV infection.
* Exception: treated and stable HBV patients with HBV DNA ≤500 IU/mL (or ≤2500 copies/mL); cured HCV patients (HCVAb+ but HCV RNA-) allowed.
* History of or active inflammatory bowel disease (Crohn's, ulcerative colitis), diverticulitis.
* Known history of allogeneic organ or stem cell transplantation.
* Interstitial lung disease or history of non-infectious pneumonitis.
* History of severe hypersensitivity to monoclonal antibodies.
* Known contraindications to cisplatin/carboplatin or paclitaxel.
* Pregnant or breastfeeding women.
* Any condition that may interfere with the study drug's safety or efficacy evaluation as judged by the investigator (e.g., other serious illness, psychiatric disorders).