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

Inclusion Criteria

• •1. Signed written informed consent prior to any trial-related procedures;
• •2. Female, aged ≥18 and ≤75 years;
• •3. ECOG PS 0-1;
• •4. Histologically or cytologically confirmed primary cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) at initial diagnosis, meeting clinical diagnostic criteria;
• •5. 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
• •6. At least one measurable lesion (including primary lesion) suitable for radiotherapy and evaluable per RECIST v1.1;
• •7. Available tumor tissue sample for biomarker assessment;
• •8. Expected survival ≥6 months;
• •9. Normal organ function (within 7 days pre-enrollment):
• •(1) Hematological criteria (no transfusion/granulocyte/platelet-stimulating drugs within 14 days):
• •1. Hemoglobin (Hb) ≥80 g/L
• •2. Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• •3. 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:
• •1. Prior immunotherapy (e.g., immune checkpoint inhibitors);
• •2. Pathological diagnosis of gastric-type adenocarcinoma;
• •3. 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;
• •4. Current use of immunosuppressants or systemic/absorbable topical corticosteroids (equivalent to \>10 mg/day prednisone) for immunosuppression, continued within 2 weeks before enrollment;
• •5. History of Grade 3-4 immune-related adverse events (irAEs) associated with prior anti-tumor immunotherapy;
• •6. Poorly controlled cardiac conditions:
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• •1. NYHA Class II or higher heart failure
• •2. Unstable angina
• •3. Myocardial infarction within 6 months
• •4. Clinically significant supraventricular/ventricular arrhythmia requiring treatment
• •5. 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.