Ivonescimab with chemotherapy before chemoradiation for high-risk locally advanced cervical cancer

Trial details

Who runs it

Women's Hospital School Of Medicine Zhejiang University

Trial code

NCT07244965

Record updated

24 November 2025

Original description

This is a single-arm, phase II clinical trial evaluating the efficacy and safety of neoadjuvant Ivonescimab combined with paclitaxel and cisplatin (TP regimen), followed by concurrent chemoradiotherapy, in patients with high-risk, locally advanced cervical cancer (FIGO stage III-IVA). Eligible participants will receive two cycles of neoadjuvant Ivonescimab plus TP chemotherapy, followed by standard concurrent chemoradiotherapy. The primary endpoints include progression-free survival (PFS) and objective response rate (ORR) following neoadjuvant treatment. Secondary endpoints include overall survival (OS), disease control rate (DCR), safety, and quality of life (EORTC QLQ-C30). Exploratory analysis will focus on identifying predictive biomarkers for Ivonescimab efficacy.Read full original descriptionShow less

Neoadjuvant Ivonescimab Combined With Paclitaxel and Cisplatin, Followed by Concurrent Chemoradiotherapy in Patients With High-Risk Locally Advanced Cervical Cancer：A Phase II, Single-Arm Study

This is a single-arm, phase II clinical trial evaluating the efficacy and safety of neoadjuvant Ivonescimab combined with paclitaxel and cisplatin (TP regimen), followed by concurrent chemoradiotherapy, in patients with high-risk, locally advanced cervical cancer (FIGO stage III-IVA). Eligible participants will receive two cycles of neoadjuvant Ivonescimab plus TP chemotherapy, followed by standard concurrent chemoradiotherapy. The primary endpoints include progression-free survival (PFS) and objective response rate (ORR) following neoadjuvant treatment. Secondary endpoints include overall survival (OS), disease control rate (DCR), safety, and quality of life (EORTC QLQ-C30). Exploratory analysis will focus on identifying predictive biomarkers for Ivonescimab efficacy.

Inclusion: 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: 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; 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); LVEF <50%; 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.

ClinicalTrials.gov NCT07244965