• Ability to understand and willingness to provide informed consent before the start of any study-specific procedures.

• Age ≥18 years old.

• A diagnosis of recurrent or metastatic HNSCC at 1 of the following sites:

∙ Nasal/paranasal sinuses

‣ Nasopharynx (Epstein-Barr virus \[EBV\] negative only)

‣ Oral cavity

‣ Oropharynx

‣ Hypopharynx

‣ Larynx

• Disease progression after treatment with PD-L1-based immune checkpoint inhibitor at any time. This can be as monotherapy or in combination with chemotherapy.

• Measurable disease according to RECIST version 1.1.

• Adequate treatment washout period of ≥21 days or 5 half-lives, whichever is shorter, for prior chemotherapy, radiotherapy, hormonal therapy, biological therapy, or immunotherapy before the first dose of study drug administration. Note: Palliative radiation is permitted but not ≤7 days before the first dose of study drug.

• ECOG PS of 0 or 1.

• Recovery from any toxic effects of previous chemotherapy, targeted therapy, or radiotherapy as judged by the investigator to Grade ≤1 (except for alopecia) according to NCI CTCAE version 5.0.

• Adequate bone marrow and organ function defined as the following:

• Bone marrow function

⁃ Absolute neutrophil count ≥1500/mm3 (growth factor administration is not permitted ≤1 week before the screening assessment)

⁃ Platelet count ≥100,000/mm3 (platelet transfusion is not permitted ≤1 week before the screening assessment)

⁃ Hemoglobin ≥8 g/dL (criteria must be met without packed red blood cell transfusion ≤1 week before the screening assessment; chronic treatment with erythropoietin is permitted if the patient is on erythropoietin for ≥8 weeks)

• Blood clotting function

• • International normalized ratio (INR) ≤1.5 × upper limit of normal (ULN) and activated partial thromboplastin time ≤1.5 × ULN (except patients who are receiving therapeutic anticoagulation and whose INR should be within the therapeutic range)

• Renal function

• •Calculated clearance (using the Cockroft-Gault formula) ≥40 mL/min/1.73 m2. Actual body weight should be used for calculating creatinine clearance. For patients with a body mass index \>30 kg/m2, lean body weight should be used instead

• Hepatic function

⁃ Total bilirubin ≤1.5 × ULN (patients with Gilbert's disease can have bilirubin \>1.5 × ULN to \<3 × ULN)

⁃ Aspartate aminotransferase/alanine aminotransferase ≤3 × ULN

⁃ An estimated life expectancy of at least 3 months based on investigator judgment.

⁃ Negative serum pregnancy test result at screening for female patients of childbearing potential.

⁃ Willingness to abide by the contraceptive requirements in Appendix 1 of the protocol.