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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Participants will receive neoadjuvant therapy consisting of Ivonescimab at 20 mg/kg administered via intravenous infusion on Day 1 of each 21-day cycle, for a total of 2 cycles. Ivonescimab will be administered in combination with paclitaxel (175 mg/m², intravenous infusion) or albumin-bound paclitaxel (260 mg/m², intravenous infusion), and cisplatin (75 mg/m², intravenous infusion) or carboplatin (AUC = 5). All chemotherapy drugs are administered on Day 1 of each cycle. The choice between cisplatin or carboplatin, and between solvent-based or albumin-bound paclitaxel, will be made at the investigator's discretion based on patient tolerance and clinical condition.
Following completion of neoadjuvant therapy, participants will undergo concurrent chemoradiotherapy consisting of weekly cisplatin (40 mg/m², intravenous infusion, once per week for 5 weeks) or carboplatin (AUC = 2, once weekly for 5 weeks), administered concurrently with pelvic external beam radiation therapy (EBRT) and intracavitary brachytherapy. Radiotherapy will be delivered per institutional standards, including a total pelvic EBRT dose of approximately 45-50.4 Gy in 25-28 fractions and image-guided brachytherapy with a total equivalent dose of at least 80-85 Gy EQD2 to point A or tumor residual volume. The choice of chemotherapy agent and radiation technique will be determined by the investigator based on clinical condition and institutional protocol.
Women's Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
Progression-Free Survival (PFS) Assessed by RECIST v1.1
Progression-Free Survival is defined as the time from the start of treatment until the first documented disease progression (based on RECIST v1.1 criteria, as assessed by the investigator) or death from any cause, whichever occurs first.
Time frame: Up to 36 months
1-Year and 3-Year Progression-Free Survival (PFS) Rate
The proportion of participants who remain progression-free at 1 year and 3 years from the start of treatment, assessed by RECIST v1.1 criteria
Time frame: 12 months and 36 months
Objective Response Rate (ORR) After Concurrent Chemoradiotherapy
The proportion of participants achieving a complete response (CR) or partial response (PR) after completing chemoradiotherapy, assessed by RECIST v1.1.
Time frame: Within 1 month after completion of chemoradiotherapy
Disease Control Rate (DCR)
The proportion of participants achieving CR, PR, or stable disease (SD) after completion of all protocol-defined treatment, based on RECIST v1.1.
Time frame: Up to 3 months post-treatment
Duration of Response (DoR)
Time from the first documented response (CR or PR) to the time of disease progression or death.
Time frame: Up to 36 months
Overall Survival (OS)
Time from treatment initiation to death from any cause.
Time frame: Up to 60 months
Safety - Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence, severity, and type of treatment-related adverse events and serious adverse events, graded according to CTCAE v5.0.
Time frame: From treatment initiation through 90 days post-treatment
Health-Related Quality of Life (HRQoL)
Change from baseline in patient-reported quality of life using the EORTC QLQ-C30 instrument.
Time frame: From baseline to 6 months post-treatment
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