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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) Assessed by RECIST v1.1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •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]
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Ivonescimab Combined With Chemotherapy (Drug)
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.
干预措施: CONCURRENT CHEMORADIATION (CISPLATIN) (Combination Product)
结局指标
主要结局
Progression-Free Survival (PFS) Assessed by RECIST v1.1
时间窗: Up to 36 months
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.
次要结局
- 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)
- Safety - Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From treatment initiation through 90 days post-treatment)
- Health-Related Quality of Life (HRQoL)(From baseline to 6 months post-treatment)