Penpulimab in Combination With Cetuximab as First-line Treatment in R/M SCCHN

This is an interventional treatment trial for Head and Neck Neoplasms Read More

Inclusion Criteria:

• Age: ≥ 18 years, male or female;
• Histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx, hypopharynx) (SCCHN);
• Recurrent/metastatic SCCHN not suitable for local treatment such as surgery or radiotherapy in the opinion of the investigator;
• At least one measurable tumor lesion according to RECIST 1.1 criteria;
• The tumor expresses PD-L1, with a comprehensive positive score CPS ≥ 1;
• Eastern Cooperative Oncology Group (ECOG) PS: 0-1
• Expected survival ≥ 3 months;
• Normal function of major organs, meeting the following criteria: blood routine examination criteria must be met: (no blood transfusion within 14 days before screening) 1) HB ≥ 90 g/L; 2) ANC ≥ 1.5 × 109/L; 3) PLT ≥ 75 × 109/L; biochemistry: (without transfusion or blood product within 14 days before screening) 1) BIL ≤ 1.5 × upper limit of normal (ULN) (≤ 3 × ULN for patients with Gilbert's syndrome); 2) ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastasis); 3) Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50ml/min (Cockcroft-Gault formula); 4) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN; left ventricular ejection fraction (LVEF) ≥ 50% assessed by cardiac Doppler ultrasound;
• Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and are willing to use reliable contraception during the trial and must be non-lactating patients; male subjects must use reliable contraception from the start of treatment to 6 months after the last dose;
• The subjects voluntarily join the study, sign the ICF, have good compliance, and cooperate in the follow-up

Exclusion Criteria:

• Received systemic chemotherapy, but excluding chemotherapy for locally advanced disease as a part of multimodal treatment. Note: Chemotherapy for locally advanced disease includes: induction chemotherapy, radiotherapy with concurrent chemotherapy and adjuvant chemotherapy;
• Previous immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways;
• Previous use of anti-EGFR drugs such as cetuximab, nimotuzumab, gefitinib, and afatinib;
• Pregnant or lactating, or planning to become pregnant during the study period;
• Current participation and receipt of study treatment, or participation in an investigational drug trial or use of an investigational device within 4 weeks prior to randomization;
• Presence of uncontrolled or symptomatic active central nervous system (CNS) metastases, which may present with clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, and/or progressive growth;
• Any active autoimmune disease or history of autoimmune disease (but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, hypophysitis, vasculitis, nephritis; positive HIV test or history of the above diseases, or history of organ transplantation; but the following patients are allowed: vitiligo, psoriasis, alopecia, well-controlled type I diabetes mellitus,Hypothyroidism with euthyroidism treated by replacement therapy;
• Treatment with systemic immunosuppressive drugs within 2 weeks before the start of study treatment or anticipation of the need for systemic immunosuppressive drugs during study treatment, with the following exceptions: 1) Intranasal, inhaled, topical steroids, or topical steroids (e.g., intra-articular); 2) Physiological doses of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent); 3) Steroid premedication for hypersensitivity (e.g., premedication for CT scan);
• Significant cardiovascular disease, such as cardiac insufficiency above class II (New York Heart Association (NYHA) classification) or left ventricular ejection fraction < 50%, unstable angina pectoris, myocardial infarction within 1 year, arrhythmia requiring treatment, QTc ≥ 450 ms (male), QTc ≥ 470 ms (female);
• The subject has an active infection or infectious disease, requiring systemic antibacterial, antifungal or antiviral treatment, including tuberculosis infection; or has an unexplained fever (body temperature > 38.5℃) during the screening period or prior to the first dose;
• Interstitial lung disease or non-infectious lung disease (including past medical history and prevalence), uncontrolled systemic diseases, including pulmonary fibrosis, acute lung disease, diabetes (fasting blood glucose (FBG) > 8.9 mmol/L), hypertension (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg), kidney disease (urine routine showed urine protein ≥ 2 +, or 24 h urine protein quantification > 1.0g), etc., except for local interstitial pneumonia induced by radiotherapy;
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
• Subjects with a history of other malignancies within the past 5 years, but cured cervical carcinoma in situ, squamous cell carcinoma of the skin, basal cell carcinoma of the skin, localized prostate cancer, or other carcinoma in situ with definitive resection;
• Virological screening meets any of the following criteria: hepatitis B HBsAg positive and HBV-DNA ≥ 10 ^ 3 copies/ml; hepatitis C: HCV antibody positive and HCV-RNA positive (results greater than the lower limit of detection of the analytical method);
• Participants may need to be vaccinated during the study or have received a live viral vaccine within 4 weeks prior to enrollment.Seasonal influenza vaccine without live virus is permitted.
• Patients with other concomitant diseases that seriously jeopardize the patient's safety or affect the patient's completion of the study, as judged by the investigator.