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

Overview

This study is a single-arm Phase II trial designed to evaluate the efficacy and safety of Docetaxel, Nimotuzumab, and Pucotenlimab combination therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma who have failed prior PD-1/PD-L1 inhibitor and platinum-based therapies, for second-line and later-line treatment.

Interventions

• Drug Drug Combination Therapy
  \[Docetaxel 75mg/m2 + Nimotuzumab 400mg + Pucotenlimab 200mg\], intravenous infusion, Day 1, every 3 weeks, for 4-6 cycles (exact number determined by investigator assessment). Maintenance Regimen: \[Nimotuzumab 400mg + Pucotenlimab 200mg\], intravenous infusion, Day 1, every 3 weeks, until protocol-defined treatment endpoints are reached. Maintenance Therapy Eligibility: Subjects who meet both criteria after the last induction cycle: No disease progression confirmed by imaging and investigato

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Imaging assessment after completion of the first 4-6 cycles of therapy (i.e.,at12-18weeks)]

Secondary outcome measures (7)

• For CPS ≥20 and the Overall Population: Median Overall Survival (mOS) [Time frame: At least up to 24 months.]
• For CPS ≥20 and the Overall Population: Median Progression-Free Survival (mPFS) [Time frame: At least up to 24 months.]
• PFS rates at 6 and 12 months [Time frame: PFS rates at 6 months and 12 months will be recorded separately.]
• Duration of Response (DoR) [Time frame: At least up to 24 months.]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: At least up to 24 months.]
• Quality of Life (QoL) [Time frame: Baseline, at the end of cycles 2 or 3 (each cycle is 21 days), at the end of cycles 4 or 6 (each cycle is 21 days), and within one week after the final treatment.]
• Psychological Scales Assessment as assessed by the Depression, Anxiety, and Stress Scale (DASS-21) [Time frame: Baseline, at the end of cycles 2 or 3 (each cycle is 21 days), at the end of cycles 4 or 6 (each cycle is 21 days), and within one week after the final treatment.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07354984 · 2025-FXY-390

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗