A Study of Nimotuzumab Plus Adebrelimab With Chemotherapy in Cisplatin-Ineligible Patients With Head And Neck Squamous Cell Carcinoma

A Prospective, Phase Ib/II Study of Nimotuzumab Combined With Adebrelimab and Chemotherapy for the Treatment of Patients With Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma Who Are Ineligible to High-Dose Cisplatin

This is a prospective, single-arm, Phase Ib/II clinical study to evaluate the safety and efficacy of nimotuzumab combined with adebrelimab and chemotherapy in patients with recurrent and metastatic head and neck squamous cell carcinoma who are ineligible to high-dose cisplatin treatment.

This study is a prospective, single-arm, Phase Ib/II clinical trial. Phase Ib uses a 3+3 dose escalation design, and Phase II uses a Simon two-stage design. Phase Ib explores the proper dosage of nimotuzumab to combine with adebrelimab and chemotherapy in patients with recurrent and metastatic head and neck squamous cell carcinoma who are ineligible to high-dose cisplatin treatment. Phase II explores the efficacy and safety of nimotuzumab combined with adebrelimab and chemotherapy in the same patient population. It is expected to enroll approximately 68 subjects with recurrent and metastatic head and neck squamous cell carcinoma who are ineligible to high-dose cisplatin treatment.

Inclusion Criteria:

1. Age: ≥18 years.
2. Diagnosis: Histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma, meeting the following conditions:Local treatment methods cannot achieve a cure (including cases where the patient refuses local treatment or is deemed unsuitable for local treatment by the physician, e.g., inability to tolerate anesthesia or other factors precluding local radiotherapy).No prior systemic treatment (targeted therapy, immunotherapy, and/or chemotherapy) after recurrence or metastasis.Primary nasopharyngeal carcinoma is not permitted.
3. Cisplatin Intolerance: Patients must have at least one of the following reasons for being unsuitable for cisplatin-based chemotherapy:Age >70 years.Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2.Renal function impairment (creatinine clearance <50 mL/min). If this criterion is met, the creatinine clearance standard in criterion 7 is not applicable.Severe tinnitus or hearing loss (requiring a hearing aid or showing a ≥25 dB shift at two consecutive frequencies on audiometry).Inability to receive intravenous hydration due to cardiac dysfunction or other comorbidities (left ventricular ejection fraction [LVEF] <50%).Patient refusal of cisplatin-based chemotherapy.
4. Oropharyngeal Cancer: Availability of tumor tissue for P16/HPV testing (if previously tested, retesting is not required).
5. Performance Status: ECOG PS score of 0-2.
6. Measurable Disease: At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
7. Adequate organ function：Hematology:Absolute Neutrophil Count (ANC): ≥1500/μL (1.5 × 10⁹/L),Platelets: ≥100,000/μL (100 × 10⁹/L),Hemoglobin: ≥9 g/dL (90 g/L) or ≥5.6 mmol/L.Renal:Serum Creatinine or Creatinine Clearance: Creatinine ≤1.5 × Upper Limit of Normal (ULN); if creatinine >1.5 × ULN, then creatinine clearance must be ≥60 mL/min.Hepatic:Total Bilirubin: ≤1.5 × ULN,Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤2.5 × ULN; if liver metastases are present, then ≤5 × ULN.Coagulation:International Normalized Ratio (INR) or Prothrombin Time (PT): ≤1.5 × ULN; if the patient is receiving anticoagulant therapy, PT or Partial Thromboplastin Time (PTT) must be within the therapeutic range for the anticoagulant used.
8. PD-L1 Testing: Availability of tumor tissue (from the tumor core or resected tumor) for PD-L1 testing (if previously tested, additional testing is not required).
9. Reproductive Status:Female subjects must have a negative pregnancy test within two weeks before starting study treatment and must not be breastfeeding.Female subjects must agree to use effective contraception during the study and for 6 months after the last dose of study drug.Male subjects must agree to use effective contraception during the study and for 6 months after the last dose of study drug.
10. Informed Consent: Subjects must voluntarily participate in the study, provide written informed consent, and be able to comply with the protocol-specified visits and procedures.

Exclusion Criteria:

1. Curable by Local Treatment: Patients whose disease can be cured by local treatment methods. Exceptions include cases where the patient refuses local treatment or is deemed unsuitable for local treatment by the investigator (specific reasons must be documented at enrollment).
2. Recent Local Treatment or Unresolved Adverse Events: Patients who have undergone radiotherapy or other local treatments (e.g., surgery) within 2 weeks prior to enrollment, or who have not recovered from adverse events (AEs) from prior treatments (i.e., AEs ≤ Grade 1 or returned to baseline). Exceptions include:Peripheral neuropathy ≤ Grade 2. Alopecia ≤ Grade 2.Laboratory abnormalities meeting inclusion criterion 7 (adequate organ function).
3. Recent Clinical Trial Participation: Patients who participated in another clinical trial within 4 weeks prior to enrollment (except those in the follow-up period who did not receive treatment).
4. Poor Prognosis: Patients with an estimated life expectancy of less than 3 months as assessed by the investigator, or those with rapidly progressing disease (e.g., tumor bleeding or uncontrolled tumor pain).
5. Immunosuppression: Patients diagnosed with an immunodeficiency disease within 7 days prior to enrollment, or those receiving systemic corticosteroid therapy or other immunosuppressive treatments. Exceptions include:Use of contrast agents.Corticosteroid use for managing AEs.Physiological doses of corticosteroids as determined by the investigator.
6. Other Malignancies: Patients diagnosed with another malignant tumor within 5 years prior to enrollment. Exceptions include:Cured basal cell carcinoma of the skin.Cured squamous cell carcinoma of the skin.Cervical carcinoma in situ.Breast carcinoma in situ.Other cured tumors deemed acceptable by the investigator.
7. Active CNS Metastases: Patients with known active central nervous system (CNS) metastases. Exceptions include patients with stable CNS metastases for at least 4 weeks prior to enrollment (confirmed by stable CT or MRI, no new lesions, no progression of existing lesions, resolution of neurological symptoms to baseline, and no corticosteroid use for at least 7 days). Patients with carcinomatous meningitis, regardless of stability, are excluded.
8. Active Autoimmune Disease: Patients with an active autoimmune disease requiring systemic treatment within 2 years prior to enrollment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants). Exceptions include replacement therapies (e.g., thyroxine, insulin, or physiological doses of corticosteroids for adrenal or pituitary insufficiency).
9. Organ or Tissue Transplantation: Patients who have received allogeneic tissue or solid organ transplantation.
10. Non-Infectious Pneumonitis: Patients with a history of non-infectious pneumonitis requiring corticosteroid treatment or current pneumonitis.
11. Active Infection: Patients with an active infection requiring systemic treatment.
12. Other Safety Concerns: Patients with medical conditions or histories that, in the investigator's judgment, may compromise safety or interfere with study assessments.
13. Mental Health or Substance Abuse: Patients with psychiatric disorders or substance abuse issues that may affect study compliance or cooperation.
14. Pregnancy or Reproductive Plans: Pregnant or breastfeeding women, or individuals planning to conceive from the start of the screening period until 180 days after the last dose of study drug.
15. HIV Infection: Patients with positive HIV serology or a history of HIV infection.
16. Active Hepatitis: Patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
17. Recent Live Vaccine: Patients who received a live vaccine within 30 days prior to the start of the study.