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

NCT07244965 | Not Yet Recruiting Phase 2

• 1 other identifier: PRO2024-752
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

LOCALLY ADVANCED CERVICAL CANCERS

Keywords

Ivonescimab; Cervical Cancer; Neoadjuvant; Immune Checkpoint Inhibitor; Concurrent Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 1-Year and 3-Year Progression-Free Survival (PFS) Rate

  12 months and 36 months

• Objective Response Rate (ORR) After Concurrent Chemoradiotherapy

  Within 1 month after completion of chemoradiotherapy

• Disease Control Rate (DCR)

  Up to 3 months post-treatment

• Duration of Response (DoR)

  Up to 36 months

• Overall Survival (OS)

  Up to 60 months

Other Outcomes (1)

• Identification of Predictive Biomarkers for Ivonescimab Efficacy

  From date of randomization to 1 month after completion of chemoradiotherapy (up to approximately 4 months total)

Study Arms (1)

Neoadjuvant Ivonescimab Plus Paclitaxel and Cisplatin, Followed by Chemoradiotherapy

EXPERIMENTAL

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; Combination Product: CONCURRENT CHEMORADIATION (CISPLATIN)

Interventions

Ivonescimab Combined With Chemotherapy DRUG

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.

Neoadjuvant Ivonescimab Plus Paclitaxel and Cisplatin, Followed by Chemoradiotherapy

CONCURRENT CHEMORADIATION (CISPLATIN) COMBINATION_PRODUCT

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.

Neoadjuvant Ivonescimab Plus Paclitaxel and Cisplatin, Followed by Chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The study is limited to biologically female participants due to the nature of cervical cancer, which affects individuals with a cervix.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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).
• Live vaccines within 4 weeks.
• Active or history of autoimmune diseases except for:

Sponsors & Collaborators

• Women's Hospital School Of Medicine Zhejiang University: lead

Study Sites (1)

Women's Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Drug Therapy; Cisplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Qiu Tang

  Women's Hospital School Of Medicine Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lumeng Luo

CONTACT

86-18368193927; luolumeng@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: November 24, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-06

Locations

CN (1)