• All subjects voluntarily participated in the study and signed informed consent.

• Male or female aged ≥18 years and ≤75 years.

• Expected survival time ≥3 months.

• ECOG 0-1.

• Patients with recurrent or metastatic head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma) confirmed by histopathology and/or cytology:

∙ Cohort\_A, B, and Cohort\_C Stage I patients who had failed or were intolerant to 1 or more lines of systemic therapy for recurrent or metastatic HNSCC (non-nasopharyngeal carcinoma);

‣ Cohort\_C Stage II patients who had not received any previous systemic antitumor therapy (other than induction chemotherapy, neoadjuvant, or adjuvant therapy) for recurrent or metastatic HNSCC (non-nasopharyngeal); Treatment failure was defined as disease progression during or after systemic antitumor therapy.

• Intolerance refers to the refusal of patients to continue the original regimen due to grade 3-4 adverse reactions after receiving standard treatment.

• Note: Recurrence or disease progression within 6 months after the last chemotherapy of multimodal therapy was considered as the first line of treatment.

• Consent to provide archival tumor tissue specimens (10-12 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If participants cannot provide tumor tissue samples, they can be enrolled if they meet other inclusion and exclusion criteria after the evaluation of the investigator.

• Must have at least one measurable lesion according to RECIST v1.1 definition; Lesions that had been previously treated with radiation could be included in a measurable lesion only if there was definite disease progression after radiation therapy.

• No blood transfusions and no use of cell growth factors and/or platelet-raising drugs during the 14 days prior to the screening period must be allowed, and the organ function level must meet the following criteria:

∙ Blood routine: hemoglobin (HGB) ≥ 90g/L; Absolute neutrophil count (NEUT) ≥ 1.5×10 9 /L; Platelet count (PLT) ≥ 100×10 9 /L;

‣ Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).

‣ Liver function: total bilirubin (TBIL≤1.5 ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were all ≤2.5 ULN, and AST and ALT were both ≤5.0 ULN when liver metastasis was present;

‣ coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN;

‣ no severe cardiac dysfunction with left ventricular ejection fraction ≥50%;

‣ proteinuria ≤2+ or ≤1000mg/24h.

• Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities such as ALP elevation, hyperuricemia, and hyperglycemia, as judged by the investigator, and toxicity without safety risk, such as alopecia, grade 2 peripheral neurotoxicity, or decreased hemoglobin ≥90g/L, as judged by the investigator).

⁃ For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, the serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients should take adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment.