A Single-Arm Phase II Clinical Study of Docetaxel Combined With Nimotuzumab and Pucotenlimab as Second-Line and Beyond Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, with no deterioration within 2 weeks prior to enrollment.
• Age ≥ 18 years and ≤ 75 years
• Patients with pathologically and/or radiologically confirmed recurrent or metastatic head and neck squamous cell carcinoma (including oral cavity, oropharynx, hypopharynx and larynx), who have previously failed treatment with PD-1 (L1) inhibitors and platinum-based drugs. The two types of drugs could be administered as a first-line combination regimen or sequential therapy, with the number of prior treatment lines not exceeding two. If disease progression occurs during neoadjuvant therapy, concurrent chemoradiotherapy or adjuvant therapy, or within 6 months after the discontinuation of such treatment, the medications used during neoadjuvant therapy, concurrent chemoradiotherapy or adjuvant therapy (including platinum-based drugs, anti-EGFR monoclonal antibodies, PD-1 (L1) inhibitors, etc.) shall be regarded as first-line treatment. Discontinuation or dose reduction of one drug during treatment, or replacement of platinum-based drugs, fluorouracil-based drugs or PD-1 (L1) inhibitors without disease progression shall be counted as the same line of treatment.
• At least one radiologically measurable lesion according to RECIST v1.1
• Assessed by the investigator as not amenable to local therapy (e.g., surgery ± radiotherapy)
• PD-L1 Combined Positive Score (CPS) ≥ 1
• Adequate organ function
• For women of childbearing potential, the result of serum or urine pregnancy test within 7 days prior to the first administration of the study drug shall be negative. If the urine pregnancy test result is positive or cannot be confirmed as negative, a serum pregnancy test shall be required for confirmation.
• The patient voluntarily participates in the study, signs the informed consent form, and is able to comply with the study schedule for follow-up visits, treatment plans, laboratory tests, and other research procedures.

Exclusion criteria

• A history of malignant tumor is known.
• Residual toxic reactions caused by prior anti-tumor therapy (including immunotherapy, targeted therapy, chemotherapy, radiotherapy, etc.) (excluding alopecia, fatigue and grade 2 hypothyroidism), or clinically significant laboratory test abnormalities > grade 1 (CTCAE v5.0)
• Known to have active central nervous system metastases and/or carcinomatous meningitis. Patients with treated brain metastases may participate in the study, provided that their disease is stable.
• A history of severe hypersensitivity reactions to taxanes or other monoclonal antibodies.
• Has any contraindication to the study drugs of this project (docetaxel, nimotuzumab, and camrelizumab)
• Uncontrolled pleural, peritoneal, pelvic or pericardial effusion requiring drainage at least once a month.
• Uncontrolled or poorly controlled heart diseases, including a history of congestive heart failure (CHF) ≥ Grade 2 (per CTCAE v5.0 or NYHA classification), myocardial infarction, unstable angina pectoris, ventricular tachycardia or torsades de pointes within 6 months prior to enrollment, or cardiac arrhythmias requiring treatment, such as complete left bundle branch block or third-degree atrioventricular block.
• Pulmonary embolism or deep vein thrombosis occurring within 3 months prior to the first administration of the study drug (excluding catheter-related thrombosis from implanted ports or PICC lines)
• A history of or current interstitial pneumonia, severe chronic obstructive pulmonary disease complicated with respiratory failure, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
• Any severe or uncontrolled systemic diseases, including uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg), diabetes mellitus (glycated hemoglobin (HbA1c) > 8%), etc.
• Patients with active bleeding, a history of coagulation disorders, or those receiving coumarin anticoagulant therapy.
• Known to have active hepatitis B or hepatitis C.
• Complicated with severe, uncontrolled infections, or known human immunodeficiency virus (HIV) infection (positive for HIV antibodies), or diagnosed with acquired immunodeficiency syndrome (AIDS); or with uncontrolled autoimmune diseases; or with a history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or previous solid organ transplantation.
• Active bacterial, viral, fungal, rickettsial, or parasitic infections receiving systemic anti-infective therapy (unless treated and resolved prior to the administration of the study drug)
• Live virus vaccines administered within 30 days prior to the first dose of the study drug. The use of inactivated seasonal influenza vaccines or approved COVID-19 vaccines is permitted, provided that the interval between vaccination and the first dose of the study drug is more than 1 week.
• Receiving immunology-based therapy for any reason
• Pregnant or lactating female patients.
• Any other diseases, clinically significant laboratory parameter abnormalities, severe medical or psychiatric illnesses/conditions, or substance abuse including alcoholism that, in the investigator's judgment, may compromise patient safety, study integrity, affect patient participation in the study, or interfere with the study objectives and outcome analysis.