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

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.

This is an open-label, single-arm, phase II clinical trial designed to evaluate 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 2018 stage III-IVA) who are not candidates for radical surgery. Eligible patients will receive two cycles of neoadjuvant therapy consisting of Ivonescimab (20 mg/kg, intravenous infusion on day 1) plus paclitaxel (175 mg/m² or albumin-bound paclitaxel 260 mg/m²) and cisplatin (75 mg/m²) or carboplatin (AUC = 5) every 3 weeks. Patients with hypersensitivity to solvent-based paclitaxel may receive albumin-bound paclitaxel. Chemotherapy agent selection (cisplatin vs. carboplatin) is at the discretion of the investigator based on patient clinical status and organ function. Following neoadjuvant treatment, patients will undergo concurrent chemoradiotherapy, including weekly cisplatin (40 mg/m² for 5 weeks) or carboplatin (AUC = 2), along with pelvic external beam radiation therapy (EBRT) and brachytherapy according to institutional standards. The primary endpoints of the study are progression-free survival (PFS) as assessed by investigators per RECIST v1.1 and objective response rate (ORR) following neoadjuvant therapy. Secondary endpoints include overall survival (OS), disease control rate (DCR), duration of response (DoR), time to response (TTR), 1-year and 3-year PFS rates, 3-year and 5-year OS rates, safety (incidence and severity of adverse events), and health-related quality of life (HRQoL) as assessed by EORTC QLQ-C30. Exploratory objectives include the identification of predictive biomarkers that may guide the clinical use of Ivonescimab in locally advanced cervical cancer. Patients will be followed for at least 30 days for adverse events and 90 days for serious adverse events following completion of study treatment or until the start of new anticancer therapy, whichever comes first. Immune-related adverse events will be monitored for at least 90 days regardless of subsequent treatments. Survival follow-up will occur every 3 months until study completion. This study aims to provide evidence for a potential new sequential therapeutic strategy integrating immune checkpoint blockade into the standard management of high-risk locally advanced cervical cancer