Nasopharyngeal Carcinoma Clinical Trials

• Willing to participate in the study, sign the informed consent form (ICF), and comply with study plan visits, treatment plans, laboratory tests, and other study procedures.

• Nasopharyngeal carcinoma confirmed by histopathology (differentiated or undifferentiated non-keratinous carcinoma).

• Age ≥ 18 \& ≤ 70 years.

• PS (Performance Status) score 0-1.

• Recurrent or metastatic nasopharyngeal carcinoma that has failed first-line platinum-containing standard regimen and/or second-line standard regimen failure.

• Previously received at least one line of systemic therapy. (Progression after radical concurrent chemoradiotherapy, during neoadjuvant or adjuvant therapy, or within 6 months after the end of treatment can be recorded as 1-line therapy).

• Recurrent or metastatic nasopharyngeal carcinoma that has failed anti PD-1/L1: anti PD-1/L1 exposure at least 6 weeks, and the protocol used at the time of enrollment in this study meets one of the following two points: (1) Relapse during adjuvant therapy after radiotherapy, or relapse within 6 months after the end of treatment; (2) First-line treatment phase, progression during anti PD-1/L1 treatment, or progression within 3 months after the end of anti PD-1/L1 (whether combined with chemotherapy/targeting drugs);

• At least one measurable lesion according to RECIST 1.1 criteria (the spiral CT scan diameter of the measurable lesion is ≥ 10 mm or the short diameter of the enlarged lymph node is ≥15mm ); lesions that have undergone local treatment can be selected as target lesions if there is clear evidence of significant progress compared to the end of treatment.

• All acute toxicities of previous antitumor therapy have returned to ≤ grade 1 (according to NCI-CTCAE v5.0) or reached the level specified in the inclusion/exclusion criteria. (Except for partial toxicity, such as alopecia, hair color change, nail change, fatigue, etc., which do not pose safety risks to subjects).

⁃ Adequate main organ function. a. Hematology: neutrophil absolute value (ANC) ≥1.5×10\^9/L, hemoglobin (Hb) ≥ 9.0 g/dL, platelets ≥ 100×10\^9/L; b. Liver function: bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert disease and serum bilirubin level ≤ 3 times ULN could be enrolled; patients with liver metastasis, ≤ 5 times ULN), AST and ALT ≤ 3 times ULN, and alkaline phosphatase ≤ 3 times ULN; Albumin ≥ 3 g/dL; c. International Normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 times; d. Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min according to Cockcroft-Gault formula; e. Proteinuria: urinary protein/creatinine ratio (UPC ratio) \< 1.0. If the UPC ratio is less than or equal to 0.5, no further check is required. Patients with UPC ratio \> 0.5 and those with 24-hour urinary protein \< 1000 mg could be enrolled; f. Note: The UPC ratio of random urine is a quantitative estimate of 24-hour urinary protein, and the two have a good correlation. UPC ratio can be calculated using the following formula: (a) Urinary protein/urinary creatinine (if both protein and creatinine are mg/dL); (b) (urinary protein)\*0.088/ urinary creatinine (if urinary creatinine is mmol/L).

⁃ Survival is expected to be ≥ 3 months.

⁃ Female subjects with negative blood human chorionic gonadotropin (HCG) (except for menopause and hysterectomy), female subjects of reproductive age and their partners using effective contraception during the trial period and within 6 months after the end of the last dose (e.g. Combined hormones \[containing estrogen and progesterone combined to inhibit ovulation, progesterone contraception combined to inhibit ovulation, IUD, intrauterine hormone release system, bilateral tubal ligation, vasectomy, abstinence from sex, etc.).

⁃ Male patients and their partners agree to use one of the contraceptive measures described in Article 9.