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

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).