SYS6010 vs Investigator's Choice of Monotherapy in Patients With Recurrent or Metastatic HNSCC

Prior treatment

• Prior treatment with TOP1(including ADCs);
• Adverse events from prior antitumor therapy not recovered to Grade ≤ 1 per NCI-CTCAE v6.0；
• Use of any of the medications or treatments within the specified washout period (prior to randomization )
• Patients who have a history of ILD/non-infectious pneumonitis treated with corticosteroids in the past, currently have ILD/non-infectious pneumonitis, for whom imaging examinations at screening cannot rule out ILD/non-infectious pneumonitis,
• Severe infection within 4 weeks prior to randomization, such as bacteremia requiring hospitalization, severe pneumonia, or active pulmonary tuberculosis;active systemic infections requiring antibiotics within 2 weeks prior to randomization;
• Pleural effusion or pericardial effusion requiring clinical intervention within 2 weeks prior to randomization;

Other illness

• History of another malignancy within 3 years prior to randomization
• Allergy to any component of SYS6010 or to humanized monoclonal antibodies，or to the control drugs (docetaxel, methotrexate, paclitaxel, cetuximab);
• Imaging examination suggests tumor invasion of the cervical, thoracic, and abdominal great vessels; and the investigator assessed that there was no risk of bleeding.
• History of ulcerative colitis or Crohn's disease;
• History of immunodeficiency (including positive HIV test, other acquired or congenital immunodeficiency diseases), history of allogeneic stem cell or organ transplant;
• Other conditions that the investigator deems unsuitable for participation in this clinical study (such as mental disorders, macular cystoid oedema, severe corneal disorders, uncontrolled or poorly controlled hypertension and diabetes mellitus, impaired oxygenation requiring continuous oxygen supplementation, etc.).

Lab values

• Prior EGFR mAb therapy within 4 months prior to treatment;
• History of serious cardiovascular or cerebrovascular conditions within 6 months prior to randomization, including but not limited to: Severe arrhythmias (e.g., ventricular arrhythmias requiring clinical intervention, third-degree atrioventricular block, QTcF \> 470 ms) (Fridericia formula: QTcF = QT/RR0.33, RR = 60/heart rate). Myocardial infarction, unstable angina, aortic dissection, angioplasty, or coronary artery bypass surgery. NYHA class II or higher heart failure with LVEF \< 50%.Stroke or other grade ≥ 3 cardiovascular/cerebrovascular events. pulmonary embolism;
• Previous permanent discontinuation of EGFR-targeted therapy due to skin toxicity, or currently have skin diseases requiring oral or intravenous medication;
• Active HBV or HCV infection (hepatitis B surface antigen and/or hepatitis B core antibody positive and HBV DNA copies ≥ 1×10\^4 copies/mL or ≥ 2000 IU/mL, HCV antibody positive and HCV RNA above the lower limit of detection of the analytical procedure). Note: For HBsAg-positive patients, it is recommended to start antiviral therapy before randomization, nucleoside analogues are recommended, such as entecavir, tenofovir disoproxil;

Other

• Pathologically confirmed patients with adenocarcinoma or sarcomatoid carcinoma etc.;
• Active central nervous system metastases or leptomeningeal metastasis;

• Participantss aged 18-75 years (inclusive);
• Patients with pathologically confirmed head and neck squamous cell carcinoma (HNSCC);.
• Participants have failed of platinum-based chemotherapy and PD-(L)1 inhibitors; for participants who received platinum-based chemotherapy and PD-(L)1 inhibitors in the adjuvant/neoadjuvant setting, disease recurrence or progression must have occurred within 6 months after completion of that therapy; radiographically confirmed disease progression during or after the most recent treatment regimen;
• Participants must have measurable disease according to RECIST (version 1.1);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Life expectancy of ≥ 3 months;
• Adequate major organ function (hematology, renal, liver, and coagulation) as determined by laboratory tests performed within 7 days prior to randomization;
• Sexually active fertile participants must agree to use methods of contraception during the study and at least 7 months after termination of study therapy and have a negative serum pregnancy test within 7 days prior to randomization;
• Willing to participate in the study, understand the study procedures, and sign a written informed consent form.