Pucotenlimab Plus Becotatug Vedotin in Perioperative Treatment of Locally Advanced Resectable Head and Neck Squamous Cell Carcinoma

Prior treatment

• Prior treatment with anti-PD-1, anti-PD-L1, MMAE/MMAF-based ADC agents, or other T-cell immune checkpoint inhibitors.
• Prior radiotherapy, systemic anti-tumor therapy, or other investigational therapy for head and neck cancer before study entry.
• Major surgery within 4 weeks before study entry, or not fully recovered from surgical toxicities/complications. Minor procedures (e.g., vascular access placement, percutaneous/endoscopic head/neck biopsy, tracheostomy tube exchange) are allowed.
• Receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 2 weeks before first dose.
• Prior or planned allogeneic tissue/solid organ transplantation.
• Anti-infective therapy within 2 weeks before randomization.
• Stroke or transient ischemic attack within 6 months before enrollment.
• Received live vaccine within 30 days before first study dose.

Other illness

• Head and neck cancer deemed non-resectable by the investigator.
• Active autoimmune disease requiring systemic treatment within 2 years before first dose.
• Any severe or uncontrolled systemic disease.
• Known hypersensitivity to any active ingredient or excipient of the study drugs.
• Evidence of active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• Uncontrolled or poorly controlled cardiac disease.
• Deep or intraluminal bleeding requiring interventional/surgical hemostasis or blood transfusion within 3 months, or current history of coagulopathy.
• Pulmonary embolism or deep vein thrombosis within 3 months.
• History of or current interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, bronchospasm, etc.
• History of other primary malignancy.
• Contraindications to study drugs (pucotenlimab and/or becotatug vedotin) or their excipients; severe hypersensitivity (Grade ≥3) to radiotherapy, cisplatin or its analogues.
• Any condition that the investigator considers unsuitable for participation in the trial.
• Grade ≥2 hearing impairment per CTCAE v6.0.

Lab values

• Positive serum pregnancy test or breastfeeding female.

Other

• Primary tumor originating from nasopharynx, nasal cavity, paranasal sinuses, salivary gland, thyroid/parathyroid gland, skin, or unknown primary site (squamous cell carcinoma).
• Grade ≥2 peripheral neuropathy (CTCAE v5.0).
• Radiologically detectable central nervous system metastases and/or carcinomatous meningitis.
• Uncontrolled pleural, peritoneal, pelvic effusion, or pericardial effusion.

• Life expectancy ≥ 6 months.
• Subjects with histologically confirmed, resectable Stage III-IVA head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent surgery.
• At least one extracranial measurable lesion per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• No severe cardiac dysfunction.
• Must provide tumor tissue sample not previously subjected to radiotherapy.
• Adequate organ function.
• Subjects of childbearing potential must use effective contraception during the study and for 180 days after the last dose.