Iparomlimab and Tuvonralimab Combined With Nimotuzumab in Recurrent or Metastatic NPC After First-line Treatment Failure: A Single-arm Phase IIa Clinical Trial

Iparomlimab and Tuvonralimab Combined With Nimotuzumab in Recurrent or Metastatic Nasopharyngeal Carcinoma After First-line Treatment Failure: A Single-arm Phase IIa Clinical Trial

This study aims to preliminarily explore the efficacy and safety of Iparomlimab and Tuvonralimab in combination with Nimotuzumab for the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC). It is expected to investigate a novel therapeutic regimen with improved efficacy and enhanced safety for recurrent/metastatic NPC, thereby providing robust evidence-based medical support for the application of dual-target immune checkpoint inhibitors in nasopharyngeal carcinoma therapy

Inclusion Criteria:

1. ECOG performance status score of 0-1;

2. Age 18 to 70 years;

3. Histologically confirmed nasopharyngeal carcinoma;

4. Patients with locoregional recurrence unsuitable for surgery or radiotherapy, or those who developed distant metastasis after standard comprehensive treatment, or initially diagnosed with metastatic nasopharyngeal carcinoma, provided they have experienced treatment failure with first-line cisplatin-based regimens (± PD-1 monoclonal antibody);

5. Availability of nasopharyngeal + neck MRI data prior to enrollment, with at least one measurable lesion (excluding bone metastases);

6. Willingness to provide archived tumor tissue specimens or undergo a biopsy to collect tumor tissue for PD-L1 expression level testing;

7. Laboratory test results within 7 days prior to enrollment meeting the following criteria:

   Hematology: Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L, hemoglobin (Hb) ≥ 9.0 g/dL, platelets (PLT) ≥ 100 × 10^9/L;

   Liver function: Total bilirubin < 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 × ULN;

   Renal function: Serum creatinine < 1.5 × ULN.

8. Voluntary participation with signed informed consent form.

Exclusion Criteria:

1. History of other malignancies (except adequately treated non-melanoma skin cancer, in situ carcinoma, or other cancers cured ≥5 years prior);
2. Comorbidities requiring long-term immunosuppressive therapy or systemic/local corticosteroids at immunocompromising doses;
3. Immunodeficiency diseases or history of organ transplantation (including but not limited to: interstitial pneumonia, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc.);
4. HIV-positive status; HBsAg-positive with detectable HBV DNA ≥1000 copies/mL; or HCV antibody-positive;
5. High-dose glucocorticoid use within 4 weeks prior;
6. Pregnant/lactating women or individuals of reproductive potential without effective contraception;
7. Laboratory test abnormalities beyond protocol-defined thresholds within 7 days before enrollment;
8. Significant impairment of cardiac, hepatic, pulmonary, renal, or bone marrow function;
9. Uncontrolled comorbidities or active infections;
10. Concurrent participation in other clinical trials or receipt of investigational drugs;
11. Unwillingness or inability to provide written informed consent;
12. Other contraindications to study treatment;
13. Psychiatric disorders or cognitive impairment limiting legal competency.