Iparomlimab and Tuvonralimab Combined With Platinum-Based Chemotherapy for Neoadjuvant Treatment of Cervical Cancer

Inclusion criteria

• Voluntary signing of written Informed Consent Form (ICF).
• Age ≥18 years and ≤75 years at enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma) with clinical staging by FIGO 2018 criteria: IB3, IIA2, IIB, or IIIC (parametrial invasion without reaching the pelvic wall, no vaginal lower third involvement).
• No prior systemic or local antitumor therapy (including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy) for cervical cancer prior to the first dose of study treatment.

Agreement to undergo radical hysterectomy with no surgical contraindications as judged by the investigator.

• At least one untreated measurable lesion according to RECIST v1.1.
• Consent to provide tumor tissue and peripheral blood samples during the screening period and study procedures for related research.
• Adequate organ function:

a) Hematology (no blood components or growth factor support within 7 days before study treatment): i. Absolute neutrophil count (ANC) ≥1.5×10⁹/L (1,500/mm³); ii. Platelet count ≥100×10⁹/L (100,000/mm³); iii. Hemoglobin ≥90 g/L. b) Renal: i. Calculated creatinine clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula); ii. Urine protein <2+ or 24-hour urine protein <1.0 g. c) Hepatic: i. Total bilirubin (TBil) ≤1.5×ULN; ii. AST and ALT ≤2.5×ULN; iii. Albumin (ALB) ≥28 g/L. d) Coagulation: i. INR and APTT ≤1.5×ULN (stable anticoagulation therapy allowed if parameters remain within therapeutic range).

e) Cardiac: i. Left ventricular ejection fraction (LVEF) ≥50%.

• Fertile women must have a negative urine or serum pregnancy test within 3 days before first dose. If urine test is inconclusive, serum testing is required. Contraception must be used from screening until 120 days post-treatment. Barrier methods or hormonal contraceptives (e.g., pills) are required.

• Fertile women: Not surgically sterilized (e.g., bilateral tubal ligation) or premenopausal (≥12 months amenorrhea with FSH in postmenopausal range).
• Effective contraception: Methods with <1% failure rate (e.g., hormonal contraceptives).
• Willingness and ability to comply with scheduled visits, protocols, labs, and study requirements.
• Expected survival ≥6 months.

Exclusion criteria

• Histopathological type other than cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (e.g., small cell carcinoma, clear cell carcinoma, sarcoma).
• History of other malignancies within 3 years prior to enrollment, excluding localized malignancies cured by local therapy (e.g., basal cell carcinoma, squamous cell carcinoma of the skin, or ductal carcinoma in situ of the breast).
• Simultaneous enrollment in another clinical study, unless it is an observational, non-interventional study or within the follow-up period of an interventional study.
• Non-specific immunomodulatory therapy (e.g., interleukins, interferons, thymosin, tumor necrosis factor) within 2 weeks prior to first dose; herbal or proprietary Chinese medicine with antitumor indications within 1 week prior to first dose.
• Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within the past 2 years. Replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal/pituitary insufficiency) is not considered systemic therapy.
• History of non-infectious pneumonia requiring systemic corticosteroids or current interstitial lung disease.
• Significant bleeding diathesis or coagulation dysfunction.
• Uncontrolled comorbidities, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease/gastritis, or psychiatric/social conditions impairing compliance or informed consent.
• History of myocarditis, cardiomyopathy, or malignant arrhythmias. Within 12 months prior to first dose: unstable angina, congestive heart failure, or vascular disease requiring hospitalization (e.g., surgical repair of aortic aneurysm/peripheral venous thrombosis). Within 6 months prior: esophageal-gastric varices, unhealed wounds, gastrointestinal perforation, fistula, obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding. Arterial thromboembolism, NCI CTCAE 5.0 grade ≥3 venous thromboembolism, transient ischemic attack, stroke, hypertensive crisis, or hypertensive encephalopathy. Within 1 month prior: acute exacerbation of COPD. Current hypertension uncontrolled with oral antihypertensives (SBP ≥160 mmHg or DBP ≥100 mmHg).
• Active or history of definite inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Severe infection within 4 weeks prior to first dose (including hospitalization, sepsis, or severe pneumonia). Active infection requiring systemic antimicrobial therapy within 10 days prior (excluding HBV/HCV antiviral therapy).
• Major surgery or severe trauma within 30 days prior to first dose; minor local procedures (excluding peripherally inserted central catheter placement) within 3 days prior.

History of immunodeficiency, HIV seropositivity, or current long-term systemic corticosteroid/immunosuppressant use.

• Active pulmonary tuberculosis (TB) or suspected TB requiring clinical exclusion (e.g., sputum AFB, chest X-ray).
• Active syphilis infection.
• History of allogeneic organ or hematopoietic stem cell transplantation.
• Untreated active HBV (HBsAg+ with HBV-DNA >1000 copies/mL [200 IU/mL] or above limit of detection). HBV patients must receive antiviral therapy during study. Active HCV (HCV Ab+ with HCV-RNA above limit of detection).
• Live vaccine administration within 30 days prior to first dose or planned during study.
• Known hypersensitivity to any study drug component or severe allergic reaction to other monoclonal antibodies.
• History of psychiatric disorders, substance abuse, alcoholism, or drug addiction.
• Pregnancy or lactation.
• Any disease, treatment, or laboratory abnormality that may confound study results, hinder compliance, or compromise participant safety.