ImmunoADC Therapy for Induction Conversion in Patients With Stage IVB OSCC/OPSCC

Prior treatment

• Unresolved toxicity of grade 2 or higher due to prior anticancer therapy;
• Uncontrolled hypertension or active cardiovascular disease, including cerebrovascular accident within 6 months before randomization, myocardial infarction within 6 months before randomization, unstable angina, congestive heart failure of New York Heart Association (NYHA; Appendix 5) class II or higher, or a serious arrhythmia that cannot be controlled with medication or may potentially affect study treatment;
• Participation in another clinical study within 30 days before enrollment;

Other illness

• Known grade 3-4 hypersensitivity reaction to any study treatment;
• Active severe clinical infection (\>grade 2 infection according to NCI-CTCAE version 5.0);
• Active autoimmune disease requiring systemic immunomodulatory or corticosteroid therapy for a chronic condition (e.g., disease-modifying drugs, glucocorticoids, or immunosuppressants). Replacement therapy, such as thyroxine, insulin, or physiologic glucocorticoid replacement for adrenal or pituitary insufficiency, is not considered systemic therapy;
• History of another malignancy and its treatment;
• History of radiotherapy to the maxillofacial and neck region;
• HPV-positive oropharyngeal cancer;
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Lab values

• Known history of human immunodeficiency virus (HIV) infection, or uncontrolled active hepatitis B, defined as hepatitis B surface antigen (HBsAg) positivity together with a detectable hepatitis B virus DNA (HBV-DNA) copy number above the upper limit of normal of the local laboratory at the study center;

Other

• Pregnant or breastfeeding women;

• Eastern Cooperative Oncology Group (ECOG) performance status: 0-1;
• Histopathologically confirmed oral/oropharyngeal squamous cell carcinoma, including tumors of the tongue, gingiva, buccal mucosa, floor of mouth, hard palate, retromolar trigone, base of tongue, soft palate, or parapharyngeal region;
• Clinical stage IVB (cT1-4N3M0 or cT4bN0-3M0, AJCC 8th edition);
• At least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
• Complete blood count: white blood cell count \>3,000/mm3, hemoglobin \>8 g/L, and platelet count \>80,000/mm3;
• Hepatic function: alanine aminotransferase/aspartate aminotransferase (ALT/AST) \<2.5 times the upper limit of normal (ULN), and bilirubin \<1.5 times the ULN;
• Renal function: serum creatinine \<1.5 times the ULN;
• Positive PD-L1 expression (combined positive score \[CPS\] \>=1) and positive EGFR expression (immunohistochemistry \[IHC\] 2+ or 3+);
• Written informed consent provided.