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.
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.
Cervical cancer of non-eligible histology (e.g., neuroendocrine carcinoma, sarcoma).
Evidence of distant metastasis, including inguinal lymph node metastasis or lymph node involvement above L1 vertebral level.
History of total hysterectomy (removal of uterus and cervix). Subtotal hysterectomy or cornuostomy preserving the cervix is acceptable.
Anatomical or geometric contraindications to brachytherapy.
Single group
Ivonescimab Combined With Chemotherapy
DrugParticipants 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.
CONCURRENT CHEMORADIATION (CISPLATIN)
Combination productFollowing 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.
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.
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
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.
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.
Duration of Response (DoR)
Time from the first documented response (CR or PR) to the time of disease progression or death.
Identification of Predictive Biomarkers for Ivonescimab Efficacy
To explore tumor tissue and/or blood-based biomarkers that may predict response or resistance to Ivonescimab, including but not limited to PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and gene expression profiles.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
