Iparomlimab and Tuvonralimab plus nimotuzumab for recurrent or metastatic nasopharyngeal carcinoma after first-line treatment failure

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 will try combining two immune-targeting drugs, iparomlimab and tuvonralimab, with the antibody nimotuzumab to see if it helps people with recurrent or metastatic nasopharyngeal cancer whose first-line cisplatin-based treatment has failed.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: Iparomlimab, Tuvonralimab, Nimotuzumab
• Locations: 1 site (Guangdong)
• Trial ID: NCT07101744 on ClinicalTrials.gov

What this trial studies

This is a single-arm Phase IIa trial testing a three-drug regimen (iparomlimab, tuvonralimab, and nimotuzumab) in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of first-line cisplatin-based therapy. Eligible participants are adults 18–70 with ECOG 0–1, measurable lesions on MRI (excluding bone-only disease), and available tumor tissue for PD-L1 testing. The primary focus is preliminary efficacy and safety to generate evidence on whether the combination yields meaningful tumor responses and an acceptable safety profile. The trial is conducted at Sun Yat-sen University Cancer Center and is intended as an exploratory step toward larger, controlled studies if results are promising.

Who should consider this trial

Good fit: Ideal candidates are adults 18–70 with histologically confirmed recurrent or metastatic nasopharyngeal carcinoma who have failed first-line cisplatin-based regimens, have ECOG performance status 0–1, at least one measurable lesion on MRI, and can provide tumor tissue for PD-L1 testing.

Not a fit: Patients with ECOG ≥2, significant uncontrolled organ dysfunction, only bone metastases as measurable disease, or who have not yet received and failed first-line cisplatin-based therapy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could provide a new treatment option that improves tumor control and outcomes for patients with recurrent or metastatic NPC after first-line failure.

How similar studies have performed: Combining immune checkpoint agents with targeted antibodies in NPC has shown encouraging signals in early-phase work, but dual-target checkpoint combinations with nimotuzumab are still relatively novel and need more evidence.

Eligibility criteria

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.

Where this trial is running

Guangdong

• Sun Yat-sen University Cancer Center — Guangdong, China (Recruiting)

Study contacts

• Study coordinator: hui xiao wang, Ph.D. (Doctor of Philosophy)

Conditions Nasopharyngeal Carcinoma; First-line Treatment Failure Nasopharyngeal Carcinoma; Nimotuzumab; Iparomlimab and Tuvonralimab