Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for CC

Inclusion Criteria:

1. Histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma,or cervical adenosquamous carcinoma.

2. -Arm 1 (Locally Advanced cervical cancer): Patients with locally advanced cervicalcancer classified as FIGO 2018 stages IB3, IIA2, IIB, or IIICr (lesion ≥4 cm,confirmed by MRI).

• Arm2 (cervical cancer patients desiring fertility-sparing treatment): Patientswith cervical cancer classified as FIGO 2018 stages IB2, IB3 (lesion ≤6 cm),IIA1, or IIA2 (lesion ≤6 cm) who have a strong desire to preserve fertility. 3）Planned to undergo surgical treatments of cervical cancer.

4. -Arm 1 (Locally Advanced cervical cancer): Age 18-75 years.

• Arm2 (cervical cancer patients desiring fertility-sparing treatment): Age 18-45years.

5. ECOG performance status score: 0-1. 6) No prior immunotherapy received by theparticipant. 7) Expected survival period ≥6 months. 8) Women of childbearingpotential must agree to use contraception (e.g., intrauterine device, oralcontraceptives, or condoms) during the study and for 6 months after the studyends. A negative serum or urine pregnancy test within 7 days before studyenrollment is required, and the patient must not be breastfeeding.

6. Adequate organ function as defined by the protocol, with test samples collectedwithin 7 days before the start of study treatment.

7. 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 inclusioncriteria 1) and 2).

2. Severe hypersensitivity (≥ Grade 3) to cisplatin, paclitaxel, iparomlimab andtuvonralimab, 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 studytreatment 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 isshorter) before the first dose.

6. Diagnosis of immunodeficiency or chronic systemic steroid therapy (exceeding 10 mgprednisone 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-modifyingdrugs, 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 Cvirus 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) Absoluteneutrophil 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) withoutliver 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-Pughclass B or C); d) HBsAg-positive with HBV DNA ≥2000 IU/mL (patients withHBsAg-positive and HBV DNA <2000 IU/mL must receive at least 2 weeks of anti-HBVtherapy 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 ≥++ andconfirmed 24-hour urine protein >1.0 g; c) Renal failure requiring hemodialysis orperitoneal 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 ≤100mg/d for prophylaxis); c) Any signs or history of bleeding diathesis, regardless ofseverity; d) Active gastrointestinal bleeding, evidenced by hematemesis,hematochezia, or melena within the past 3 months, without resolution confirmed byendoscopy or colonoscopy; e) Any CTCAE ≥ Grade 3 bleeding or hemorrhagic eventwithin 4 weeks before the first dose.

21. Cardiovascular and cerebrovascular abnormalities: a) Any of the following within 12months 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 heartfailure, cerebrovascular accident, or transient ischemic attack; b) Deep veinthrombosis or pulmonary embolism within 6 months before the first dose; c) Leftventricular ejection fraction (LVEF) <50% assessed by Doppler ultrasound; d) AverageQTc interval corrected by Fridericia's formula (QTcF) (based on at least 3consecutive ECG readings): ≥470 ms for females; e) Uncontrolled hypertension (atleast 2 measurements showing systolic blood pressure ≥150 mmHg or diastolic bloodpressure ≥100 mmHg).

22. Other factors judged by the investigator as potentially affecting study results orleading to premature termination, such as alcoholism, drug abuse, other severediseases (including mental illness) requiring concurrent treatment, significantlaboratory abnormalities, or family/social factors that may compromise patientsafety.