Patients with high-risk locally advanced cervical cancer who have not received prior anti-tumor therapy, with histological types including squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
Conditions
Interventions
Ivonescimab plus TP neoadjuvant chemotherapy group:Ivonescimab in combination with paclitaxel and cisplatin as neoadjuvant therapy, followed by concurrent chemoradiation
Sponsors
Women’s Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The participant is able to understand and voluntarily sign a written informed consent form (ICF). The ICF must be signed prior to performing any study-specific procedures required by the protocol. 2. Female participants aged >= 18 years on the date of signing the informed consent form. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Estimated life expectancy >= 3 months. 5. Histologically confirmed cervical cancer. 6. Histologic subtypes limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. 7. No prior anti-tumor therapy, including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, or immunotherapy. Note: Pelvic lymph node or para-aortic lymph node dissection or biopsy performed solely for clinical staging purposes is permitted. 8. FIGO 2018 stage III–IVA disease considered unsuitable for radical surgery. Lymph node metastasis may be diagnosed by biopsy or by imaging. Imaging-based diagnosis of lymph node metastasis must meet the following: • MRI or CT showing a positive lymph node with short-axis diameter >= 10 mm; • To qualify as a target lesion, the short-axis diameter must be >= 15 mm. 9. At least one measurable lesion according to RECIST v1.1 criteria. 10. Tumor PD-L1 CPS >= 1. 11. All participants must provide tumor tissue samples prior to initiation of study treatment, including: • A formalin-fixed, paraffin-embedded (FFPE) tissue block, or • At least five unstained tumor tissue slides, preferably freshly obtained. 12. Adequate organ function as demonstrated by screening laboratory results: a. Hematologic function (No blood component transfusion or growth factor support allowed within 2 weeks prior to treatment initiation) • Absolute neutrophil count (ANC) >= 1.5 × 10?/L • Platelet count >= 90 × 10?/L • Hemoglobin >= 9.0 g/dL b. Renal function • Serum creatinine = 1.5 × ULN, or • Calculated creatinine clearance (CrCl) >= 50 mL/min • If cisplatin is planned, CrCl must be >= 60 mL/min. CrCl is calculated using the Cockcroft–Gault formula: \text{CrCl (mL/min)} = \frac{(140 - \text{age}) \times \text{weight (kg)} \times 0.85}{72 \times \text{serum creatinine (mg/dL)}} c. Hepatic function • Total bilirubin (TBil) = 12 consecutive months without menses for a non-medical reason and FSH within the postmenopausal reference range. b. Highly effective contraceptive methods:Failure rate < 1% per year when used consistently and correctly. Meth
Exclusion criteria
Exclusion criteria: 1. Histologic subtypes of cervical cancer other than those permitted, including neuroendocrine carcinoma, sarcoma, or other rare variants. 2. Evidence of distant metastasis, including inguinal lymph node metastasis or lymph node involvement above the L1 vertebral level. 3. Prior total hysterectomy (removal of both uterine corpus and cervix). Subtotal hysterectomy or cornual resection that preserves the cervix is allowed. 4. Anatomical abnormalities or tumor geometry that preclude the use of brachytherapy. 5. History of other active malignancies within 2 years, except for malignancies considered locally curable and currently disease-free (e.g., cutaneous squamous cell carcinoma, basal cell carcinoma, superficial bladder cancer, ductal carcinoma in situ). Note: Participants with a history of cervical carcinoma in situ must be excluded. 6. Clinically significant bilateral hydronephrosis that, in the investigator’s judgment, cannot be relieved by nephrostomy or ureteral stent placement. 7. Receipt of any anti-tumor therapy within 2 weeks prior to first dose, including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, immunotherapy, or any treatment targeting immune co-stimulatory pathways (e.g., antibodies against ICOS, CD40, CD137, GITR, OX40). 8. Use of immunomodulatory agents (e.g., thymosin, interferon, interleukin-2) within 2 weeks prior to study treatment. 9. Systemic corticosteroids (>10 mg/day prednisone or equivalent) or other systemic immunosuppressive drugs within 2 weeks prior to treatment initiation, except for: a. Inhaled, ophthalmic, or topical corticosteroids = II. c. Severe arrhythmias requiring long-term medical management. Asymptomatic, rate-controlled atrial fibrillation is allowed. d. Cerebrovascular accident (CVA) within 6 months prior to treatment. e. Left ventricular ejection fraction (LVEF) < 50%. f. History of myocarditis or cardiomyopathy. 16. Known primary or secondary immunodeficiency, including HI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS);Objective response rate (ORR) after neoadjuvant therapy;Objective response rate (ORR) after concurrent chemoradiotherapy; | — |
Secondary
| Measure | Time frame |
|---|---|
| 3-year progression-free survival rate;Safety and tolerability (adverse events and laboratory abnormalities);Health-related quality of life assessed by EORTC QLQ-C30;1-year progression-free survival rate;Overall survival (OS); | — |
Countries
China
Contacts
Public ContactQiu Tang
Women’s Hospital, Zhejiang University School of Medicine
Outcome results
None listed