Evaluation of AK104 (Cadonilimab) Combined with Chemotherapy for Recurrent or Metastatic Small Cell Neuroendocrine Carcinoma of the Cervix

Inclusion Criteria:

1. Voluntarily sign a written Informed Consent Form (ICF).

2. Female participants aged ≥18 years and ≤75 years at the time of enrollment.

3. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.

4. Histologically or cytologically confirmed small cell neuroendocrine carcinoma of thecervix, classified as recurrent or metastatic, with no prior systemic therapy forthe recurrent or metastatic stage. Recurrent patients must be assessed by theinvestigator as unsuitable for surgery or radiotherapy.

5. At least one untreated measurable lesion according to RECIST v1.1.

6. Adequate organ function: a) Hematologic (no use of any blood components or growth factor support within 7days before starting study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L (1,500/mm³); ii. Platelet count ≥ 100 × 10^9/L (100,000/mm³); iii. Hemoglobin ≥ 90 g/L. b) Renal: i. Estimated creatinine clearance (CrCl) ≥ 50 mL/min.

• CrCl will be calculated using the Cockcroft-Gault formula: CrCl (mL/min) = {(140 - age) × weight (kg) × 0.85} / (serum creatinine (mg/dL) × 72). ii. Urine protein < 2+ or 24-hour urine protein < 1.0 g. c) Hepatic: i. Serum totalbilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 2.5 × ULN; iii. Serum albumin (ALB) ≥ 28 g/L. d) Coagulation: i. International normalized ratio (INR) and activatedpartial thromboplastin time (APTT) ≤ 1.5 × ULN (participants receivinganticoagulation therapy must be on a stable dose, and coagulation parameters (PT/INRand APTT) should be within the expected therapeutic range at screening). e) Cardiac function: i. Left ventricular ejection fraction (LVEF) ≥ 50%.

7. Female participants of childbearing potential must have a negative urine or serumpregnancy test within 3 days prior to the first dose (if the urine pregnancy testresult cannot be confirmed as negative, a serum pregnancy test is required, and theserum result will prevail). If a female participant of childbearing potential issexually active with a non-sterilized male partner, she must use acceptablecontraception starting from screening and agree to continue using contraception for 120 days after the last dose of the study drug; discontinuation of contraceptionafter this point should be discussed with the investigator.

8. Participants must be willing and able to comply with the scheduled visits, treatmentplans, laboratory tests, and other requirements of the study.

Exclusion Criteria:

1. Other pathological histological types (e.g., squamous cell carcinoma,adenocarcinoma, adenosquamous carcinoma, clear cell carcinoma, sarcoma, etc.).

2. Malignant tumors other than small cell neuroendocrine carcinoma of the cervix within 3 years before enrollment. Participants with other malignancies cured by localtreatment, such as basal or squamous cell carcinoma of the skin, superficial bladdercancer, or carcinoma in situ of the breast, are not excluded.

3. Concurrent enrollment in another clinical study, unless it is an observational,non-interventional study or the follow-up phase of an interventional study.

4. Active autoimmune disease requiring systemic treatment within 2 years prior to thestart of study treatment, or autoimmune disease that is likely to recur or requireplanned treatment as judged by the investigator; exceptions include: skin diseasesnot requiring systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema);hypothyroidism due to autoimmune thyroiditis requiring only a stable dose of hormonereplacement therapy; well-controlled type 1 diabetes mellitus; childhood asthma thathas completely resolved without adult intervention; diseases judged by theinvestigator as unlikely to recur in the absence of external triggers.

5. Active or clinically required treatment of inflammatory bowel disease (e.g., Crohn'sdisease, ulcerative colitis, or chronic diarrhea).

6. Requirement for systemic corticosteroids (>10 mg prednisone equivalent per day) orother immunosuppressive drugs within 14 days after taking the study drug. In theabsence of active autoimmune disease, inhaled or topical steroids and adrenalreplacement doses >10 mg prednisone equivalent per day are allowed. Participants areallowed to use topical, ocular, intra-articular, intranasal, and inhaledcorticosteroids (with minimal systemic absorption). Physiologic replacement doses ofsystemic corticosteroids are allowed even if >10 mg/day of prednisone equivalent.Short-term use of corticosteroids for prevention (e.g., contrast allergy) ortreatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions dueto contact allergens) is permitted.

7. Prior treatment with immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1,anti-CTLA-4), immune checkpoint agonists (e.g., antibodies against ICOS, CD40,CD137, GITR, OX40), immune cell therapies, or any treatment targeting tumorimmunomodulatory mechanisms.

8. Known history of human immunodeficiency virus (HIV) or positive test for acquiredimmune deficiency syndrome (AIDS).

9. Known history of allogeneic organ transplant or allogeneic hematopoietic stem celltransplantation.

10. Known history or presence of interstitial lung disease.

11. History of gastrointestinal perforation and/or fistula within 6 months prior toenrollment.

12. Necrotic lesions identified within 4 weeks before enrollment, with a risk of majorhemorrhage as judged by the investigator.

13. Severe infection within 4 weeks before the first dose, including but not limited tocomplications requiring hospitalization, sepsis, or severe pneumonia.

14. Known active tuberculosis (TB). Participants suspected of having active TB should beexcluded based on chest X-ray, sputum examination, and clinical symptoms and signs.

15. Untreated chronic hepatitis B or hepatitis B virus (HBV) carriers with HBV DNA >1000IU/mL, and participants with active hepatitis C should be excluded. Non-activehepatitis B surface antigen (HBsAg) carriers, participants with stable hepatitis Bafter treatment (HBV DNA <1000 IU/mL), and cured hepatitis C participants can beenrolled. Participants positive for HCV antibodies are eligible only if HCV RNA isnegative.

16. Receipt of the last radiotherapy or antitumor therapy (e.g., chemotherapy, targetedtherapy, herbal medicine for tumor control, tumor embolization) within 4 weeksbefore the first dose of AK104.

17. Major surgery within 30 days prior to the first dose of AK104, or failure to recoverfully from prior surgery. Local surgery (e.g., placement of a central venous port,core needle biopsy, prostate biopsy) is allowed, provided it is completed at least 24 hours before the first dose of study medication.

18. Known history or presence of meningeal metastasis, spinal cord compression,leptomeningeal disease, or active brain metastases. However, participants who meetthe following requirements and have measurable lesions outside the central nervoussystem may be enrolled: 1) Previously untreated, currently asymptomatic (e.g., noneurological impairment, seizures, or other typical CNS metastasis symptoms andsigns; no corticosteroid treatment required); 2) Asymptomatic after treatment withradiographic stability for at least 4 weeks before the start of study treatment (e.g., no new or enlarged brain metastases) and cessation of systemiccorticosteroids and antiepileptic therapy for at least 2 weeks.

19. Participants with pleural effusion, pericardial effusion, or ascites that cannot becontrolled stably despite repeated drainage or other methods as determined by theinvestigator.

20. Uncontrolled comorbidities, including symptomatic congestive heart failure (New YorkHeart Association Classification of Functional Status Class 3 or 4), uncontrolledhypertension, unstable angina, poorly controlled arrhythmias, evidence of acute oractive myocardial ischemia, severe active peptic ulcer disease or gastritis, orpsychiatric/psychosocial conditions that may limit compliance with studyrequirements or affect the ability to provide written informed consent. Any arterialthromboembolism, including myocardial infarction, cerebrovascular accident, ortransient ischemic attack, within 6 months prior to enrollment, history of deep veinthrombosis, pulmonary embolism, or other serious thromboembolic events.

21. Unresolved toxicity from prior antitumor treatment, defined as toxicity notrecovered to Grade 0 or 1 by NCI CTCAE version 5.0, or to the level specified in theinclusion/exclusion criteria, except for alopecia. Participants with irreversibletoxicity not expected to be exacerbated by study drug administration (e.g., hearingloss) may be included after consultation with the medical monitor. Participants withirreversible radiation-induced late toxicity may be included after consultation withthe medical monitor.

22. Receipt of a live vaccine within 30 days before the first dose of AK104, or plannedreceipt of a live vaccine during the study.

23. Known history of severe hypersensitivity to other monoclonal antibodies.

24. Known allergy to any components of the AK104 formulation.

25. Pregnant or breastfeeding women.

26. Any condition that, in the opinion of the investigator, may pose a risk to theparticipant receiving study medication, interfere with the evaluation of studymedication, or compromise participant safety or study results.