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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: LOCALLY ADVANCED CERVICAL CANCERS
• Intervention / Treatment: Drug: Ivonescimab Combined With Chemotherapy; Combination product: CONCURRENT CHEMORADIATION (CISPLATIN)

Detailed Description

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
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lumeng Luo; Phone Number: 86-18368193927; Email: luolumeng@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Women's Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 Criteria:

• 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.
• 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).
• Bilateral hydronephrosis deemed non-relievable by nephrostomy or ureteral stenting.
• 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
• Physiologic hormone replacement ≤10 mg/day prednisone or equivalent
• 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.
• 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.
• Active or history of autoimmune diseases except for:
• Vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy
• 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
• LVEF <50%
• 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.
• Known contraindications to cisplatin/carboplatin or paclitaxel.
• Pregnant or breastfeeding women.
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Ivonescimab Plus Paclitaxel and Cisplatin, Followed by Chemoradiotherapy; Participants in this arm will receive two cycles of neoadjuvant therapy consisting of Ivonescimab (20 mg/kg, intravenous infusion on Day 1 of each 21-day cycle) combined with paclitaxel (175 mg/m² or albumin-bound paclitaxel 260 mg/m²) and either cisplatin (75 mg/m²) or carboplatin (AUC = 5), at the discretion of the investigator. After completion of neoadjuvant treatment, participants will undergo concurrent chemoradiotherapy with weekly cisplatin (40 mg/m² × 5 weeks) or carboplatin (AUC = 2), in combination with pelvic external beam radiation therapy (EBRT) and brachytherapy per institutional protocol.

Drug: Ivonescimab Combined With Chemotherapy; 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.; Combination product: CONCURRENT CHEMORADIATION (CISPLATIN); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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.	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.	Up to 36 months
Overall Survival (OS)	Time from treatment initiation to death from any cause.	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.	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.	From baseline to 6 months post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From date of randomization to 1 month after completion of chemoradiotherapy (up to approximately 4 months total)

Collaborators and Investigators

• Sponsor: Women's Hospital School Of Medicine Zhejiang University
• Investigators: Principal Investigator: Qiu Tang, Women's Hospital School of Medicine Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: August 25, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Cervical Cancer; Neoadjuvant; Immune Checkpoint Inhibitor; Concurrent Chemoradiotherapy; Ivonescimab
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin; Drug Therapy
• Other Study ID Numbers: PRO2024-752

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No