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

Korábbi kezelés

• 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
• 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.
• Vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy

Más betegség

• Cervical cancer of non-eligible histology (e.g., neuroendocrine carcinoma, sarcoma).
• History of total hysterectomy (removal of uterus and cervix). Subtotal hysterectomy or cornuostomy preserving the cervix is acceptable.
• 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).
• 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.
• Active or history of autoimmune diseases except for:
• 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
• 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.
• 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).

Laborértékek

• LVEF <50%

Egyéb

• Evidence of distant metastasis, including inguinal lymph node metastasis or lymph node involvement above L1 vertebral level.
• Anatomical or geometric contraindications to brachytherapy.
• Bilateral hydronephrosis deemed non-relievable by nephrostomy or ureteral stenting.
• Physiologic hormone replacement ≤10 mg/day prednisone or equivalent
• Known contraindications to cisplatin/carboplatin or paclitaxel.
• Pregnant or breastfeeding women.

• 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.