Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembrolizumab for the Treatment of SCCHN

Exclusion Criteria

• •1. Primary tumour site (any histology) of nasopharynx, nasal cavity, sinuses, salivary glands, thyroid or parathyroid glands, skin, or unknown primary site of tissue origin.
• •2. Patient with malignancies other than HNSCC within 3 years prior to enrolment. Patients with other tumours that have been cured through local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded.
• •3. Concurrent enrolment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study; Received study treatment within 4 weeks prior to randomization.
• •4. Prior treatment with systemic anti-angiogenic drugs.
• •5. Previous head and neck re-irradiation for recurrent/metastatic disease
• •6. Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibody, anti- CTLA-4 antibody, anti-TIGIT antibody, anti-LAG3 antibody, anti-CD47, anti-SIRPα, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any other treatment that targets tumour immunity including therapeutic tumour vaccine, and other adjuvant/neoadjuvant anti-PD-1 based therapy.
• •7. Patients with ulcers on the skin surface related to the current cancer during the screening period, superficial or protruding skin lesions with excessive surface tension and a greater risk of ulceration, or other patients with a greater risk of ulceration as assessed by the investigator. Patients with recent tracheostomy involving the tumour which are at risk of bleeding.
• •8. Imaging during the screening period shows that the tumour invades/infiltrates the surrounding important organs (such as trachea, oesophagus, and based on investigator assessment ofbleeding risk) and/or large blood vessels in the neck (such as subclavian artery, common internal and/or external carotid artery, etc.) or if the investigator judges that entering the study might cause a potential risk of bleeding.
• •9. Presence of brainstem, meningeal metastases, spinal cord metastases or compression, or leptomeningeal disease.
• •10. Received curative head and neck radiotherapy within 6 months prior to randomization. Palliative local treatment for non-head and neck areas carried out within 3 weeks before randomization; Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymus peptide, tumour necrosis factor, etc.) within 2 weeks prior to randomization, excluding IL-11 for the treatment of thrombocytopenia.
• •11. Presence of active autoimmune disease requiring systemic therapy (e.g., treatment with disease-modifying drugs, corticosteroids, immunosuppressants) within 2 years prior to randomization. Alternative therapies (e.g., thyroxine, insulin, or those targeting the adrenal glands or pituitary) and physiologic corticosteroid replacement therapy for pituitary insufficiency are not considered systemic treatment.
• •12. History of immunodeficiency; Those who have history of positive test for HIV antibodies; Current long-term use of systemic corticosteroids or other immunosuppressants is excluded.
• •13. Previous or current non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy, or current presence of lung diseases including but not limited to the following: pneumoconiosis, silicosis, drug-related pneumonia, pulmonary diseases with severe impairment of lung function, etc.
• •14. Severe infection within 4 weeks prior to randomization, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active non-severe infection that has received systemic anti-infective therapy within 2 weeks prior to randomization.