Ivonescimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy Followed by Type A Hysterectomy in Stage IB2 and IIA1 Cervical Cancer

Summary

Cervical cancer ranks fourth globally in both incidence and mortality rates, making early diagnosis and treatment of great significance. For early-stage cervical cancer, surgery remains the primary treatment approach. According to the latest NCCN guidelines, patients with Stage IA2 or IB1 cervical cancer confirmed by cone biopsy who meet Concerv or SHAPE criteria no longer require type C/B hysterectomy. Instead, they may undergo type A hysterectomy with reduced surgical margins. However, patients with Stage IB2 or IIA1 tumors measuring 2-4 cm still require radical hysterectomy (type C). Radical hysterectomy carries high risks of postoperative complications and significantly impairs quality of life, including major vascular injury, urinary tract damage and dysfunction, lymphatic complications, and sexual dysfunction. Therefore, there is an imperative need to explore alternative or refined treatment approaches for Stage IB2/IIA1 cervical cancer that ensure survival outcomes while reducing surgical morbidity and improving quality of life. Neoadjuvant therapy followed by scale-reduced surgery may represent a feasible strategy. Both immune escape and angiogenesis are core drivers of tumorigenesis and progression. Combined immunotherapy and anti-angiogenic therapy have demonstrated favorable antitumor efficacy and manageable safety profiles across multiple tumor types. Ivonescimab is a novel humanized tetrameric IgG-scFv bispecific antibody targeting PD-1 and VEGF. Mechanistically, PD-1 blockade reverses T-cell suppression while VEGF inhibition curbs neovascularization, yielding synergistic therapeutic enhancement. This agent has shown promising efficacy and safety in advanced non-small cell lung cancer, hepatocellular carcinoma, and recurrent glioblastoma, though clinical data in cervical cancer remain absent. Therefore, this prospective exploratory study aims to evaluate the efficacy and safety of neoadjuvant Ivonescimab combined with paclitaxel and cisplatin followed by type A hysterectomy for stage IB2/IIA1 cervical cancer. The findings may provide novel insights for optimizing treatment paradigms-ensuring survival outcomes while preserving quality of life.

Eligibility

Inclusion Criteria:

(1)Patients with FIGO 2018 stages IB2, IIA1 (2\< lesion ≤4 cm, confirmed by MRI); (2) Histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma; (3)18-75 years old. (4) ECOG performance status score: 0-1. (5) No prior therapy received by the participant. (6)Expected survival period ≥6 months. (7) Women of childbearing potential must agree to use contraception (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 6 months after the study ends. A negative serum or urine pregnancy test within 7 days before study enrollment is required, and the patient must not be breastfeeding.

(8) Adequate organ function as defined by the protocol, with test samples collected within 7 days before the start of study treatment.

(9) Participants voluntarily join the study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Histological subtypes or disease stages other than those permitted in inclusion criteria (1) and (2).
2. Severe hypersensitivity (≥ Grade 3) to cisplatin, paclitaxel, Ivonescimab , and/or any of their excipients.
3. Participation in another clinical trial within 4 weeks prior to enrollment.
4. Administration of inactivated vaccines within 30 days before the first study treatment or planned vaccination during the study period.
5. Treatment with systemic immunostimulants, colony-stimulating factors, interferons, interleukins, or combination vaccines within 6 weeks or 5 half-lives (whichever is shorter) before the first dose.
6. Diagnosis of immunodeficiency or chronic systemic steroid therapy (exceeding 10 mg prednisone equivalent per day) or any other form of immunosuppressive therapy within 7 days before the first dose.
7. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within the past 2 years.
8. History of (non-infectious) pneumonitis requiring steroid treatment or current (non-infectious) pneumonitis.
9. Active infection requiring systemic treatment.
10. Known history of HIV infection.
11. Known history of hepatitis B (defined as HBsAg reactivity) or active hepatitis C virus infection (defined as detectable HCV RNA \[qualitative\]).
12. Known history of active tuberculosis (TB; Mycobacterium tuberculosis).
13. Prior allogeneic tissue/solid organ transplantation.
14. Central nervous system metastases, such as brain metastases.
15. Uncontrolled pleural or peritoneal effusion.
16. Impaired mobility due to pathological fractures caused by bone metastases.
17. Insufficient bone marrow function (without transfusion within 14 days): a) Absolute neutrophil count (ANC) \<1.5×10⁹/L;b) Platelets \<100×10⁹/L; c) Hemoglobin \<9 g/dL.
18. Liver abnormalities: a) ALT, AST, or ALP \>2.5× upper limit of normal (ULN) without liver metastasis or \>5×ULN with liver metastasis; b) Total bilirubin \>1.5×ULN (\>3×ULN in patients with Gilbert's syndrome); c) Decompensated cirrhosis (Child-Pugh class B or C); d) HBsAg-positive with HBV DNA ≥2000 IU/mL (patients with HBsAg-positive and HBV DNA \<2000 IU/mL must receive at least 2 weeks of anti-HBV therapy before the first dose); e) HCV antibody-positive with detectable HCV RNA.
19. Kidney abnormalities: a) Serum creatinine \>1.5×ULN or estimated creatinine clearance \<60 mL/min using the Cockcroft-Gault formula; b) Urinalysis showing protein ≥++ and confirmed 24-hour urine protein \>1.0 g; c) Renal failure requiring hemodialysis or peritoneal dialysis; d) History of nephrotic syndrome.
20. Bleeding risk: a) Coagulation abnormalities: Activated partial hromboplastin time (APTT) or thrombin time (TT) \>1.5×ULN, or international normalized ratio (INR) \>1.5 (\>2.5 for patients requiring anticoagulation therapy); b) History of bleeding (e.g., hemoptysis), coagulation disorders, or current use of warfarin, aspirin, low-molecular-weight heparin, or other antiplatelet agents (except for aspirin ≤100 mg/d for prophylaxis); c) Any signs or history of bleeding diathesis, regardless of severity; d) Active gastrointestinal bleeding, evidenced by hematemesis, hematochezia, or melena within the past 3 months, without resolution confirmed by endoscopy or colonoscopy; e) Any CTCAE ≥ Grade 3 bleeding or hemorrhagic event within 4 weeks before the first dose.
21. Cardiovascular and cerebrovascular abnormalities: a) Any of the following within 12 months before the first dose: ≥ Grade 2 myocardial ischemia, yocardial infarction, arrhythmias, ≥ Grade 3 cardiac insufficiency, uncontrolled angina, coronary/peripheral artery bypass graft surgery, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack; b) Deep vein thrombosis or pulmonary embolism within 6 months before the first dose; c) Left ventricular ejection fraction (LVEF) \<50% assessed by Doppler ultrasound; d) Average QTc interval corrected by Fridericia's formula (QTcF) (based on at least 3 consecutive ECG readings): ≥470 ms for females; e) Uncontrolled hypertension (at least 2 measurements showing systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
22. Other factors judged by the investigator as potentially affecting study results or leading to premature termination, such as alcoholism, drug abuse, other severe diseases (including mental illness) requiring concurrent treatment, significant laboratory abnormalities, or family/social factors that may compromise patient safety.

Conditions2

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