Iparomlimab and Tuvonralimab With Chemoradiation for the Treatment of Locally Recurrent and Oligometastatic Cervical Cancer

Inclusion criteria

• Signed written informed consent prior to any trial-related procedures;
• Female, aged ≥18 and ≤75 years;
• ECOG PS 0-1;
• Histologically or cytologically confirmed primary cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) at initial diagnosis, meeting clinical diagnostic criteria;
• Locally recurrent or oligometastatic cervical cancer after initial treatment. Total recurrent + metastatic lesions ≤5.Oligometastasis criteria:Lymph node metastases within the same region = 1 lesion;Liver metastases ≤1 lesion;Lung metastases ≤3 lesions
• At least one measurable lesion (including primary lesion) suitable for radiotherapy and evaluable per RECIST v1.1;
• Available tumor tissue sample for biomarker assessment;
• Expected survival ≥6 months;
• Normal organ function (within 7 days pre-enrollment):

(1) Hematological criteria (no transfusion/granulocyte/platelet-stimulating drugs within 14 days):

• Hemoglobin (Hb) ≥80 g/L
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Platelets (PLT) ≥50×10⁹/L (2) No functional organic disease:

a) ALT/AST ≤2.5×ULN, total bilirubin ≤1.5×ULN, ALP ≤3×ULN, albumin ≥30 g/L b) Serum Cr ≤1.5×ULN (if >1.5×ULN, CrCl ≥50 mL/min by Cockcroft-Gault formula) c) PT prolongation ≤6 sec, APTT ≤1.5×ULN d) TSH ≤ULN (if abnormal, FT3/FT4 must be normal) f) LVEF >50% 10. Prior anti-tumor treatment toxicities recovered to ≤Grade 1 (CTCAE v5.0) pre-treatment, excluding:

• Alopecia/pigmentation (any grade)
• Peripheral neuropathy (≤Grade 2)
• Other toxicities where benefit-risk favors treatment 11. Non-sterilized/childbearing-potential females must:
• Use medical contraception (IUD/oral contraceptives/condoms) during treatment + 3 months post-treatment
• Negative serum/urine HCG within 7 days pre-enrollment
• Non-lactating 12. Expected compliance with protocol follow-up following criteria:

• Prior immunotherapy (e.g., immune checkpoint inhibitors);
• Pathological diagnosis of gastric-type adenocarcinoma;
• Active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Exceptions: vitiligo; childhood asthma fully resolved without intervention in adulthood. Exclusion: asthma requiring bronchodilator therapy;
• Current use of immunosuppressants or systemic/absorbable topical corticosteroids (equivalent to >10 mg/day prednisone) for immunosuppression, continued within 2 weeks before enrollment;
• History of Grade 3-4 immune-related adverse events (irAEs) associated with prior anti-tumor immunotherapy;
• Poorly controlled cardiac conditions:

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• NYHA Class II or higher heart failure
• Unstable angina
• Myocardial infarction within 6 months
• Clinically significant supraventricular/ventricular arrhythmia requiring treatment
• QTc >450 ms (males) or >470 ms (females); 7. Coagulation abnormalities (INR >1.5 or PT >16 s), bleeding tendency, or current thrombolytic/anticoagulant therapy; 8. Prior radiotherapy/chemotherapy/hormonal therapy/surgery/targeted therapy completed <4 weeks before study treatment (or <5 drug half-lives, whichever is longer); unresolved toxicities (excluding alopecia) from prior therapies >CTCAE Grade 1; 9. Poorly controlled third-space effusion requiring drainage before first trial drug administration; 10. Significant hemoptysis (≥2.5 mL/day) within 2 months before randomization; 11. Known hereditary/acquired bleeding/thrombotic disorders (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism); 12. Active infection or unexplained fever >38.5°C during screening/before first dose; 13. Objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction; 14. Immunodeficiency (e.g., HIV infection) or active hepatitis:

• HBV DNA > upper limit of normal (ULN)
• HCV RNA > ULN; 15. Use of other investigational drugs within 4 weeks before first dose; radiotherapy/local therapy within 2 weeks without full recovery; 16. Concurrent/prior malignancies (except cured basal cell carcinoma/cervical carcinoma in situ); 17. Planned concurrent systemic anti-tumor therapy during the study; 18. Live vaccination within 4 weeks before treatment or planned during the study; 19. Other conditions potentially requiring study termination per investigator judgment:
• Severe comorbidities (including psychiatric disorders) requiring treatment
• Critical lab abnormalities
• Social/family factors compromising safety or data/sample collection.