Chidamide in Combination With Toripalimab and Anlotinib in Recurrent/Metastatic Nasopharyngeal Carcinoma.

Inclusion criteria

• 1. Age: ≥18 years and ≤70 years, gender unrestricted. 2. Diagnosis: Histologically/pathologically confirmed metastatic nasopharyngeal carcinoma (NPC) that has failed at least one prior line of therapy (including cisplatin-containing regimens) or is intolerant to existing therapies (relapse within 6 months after completion of adjuvant/neoadjuvant concurrent chemoradiotherapy is eligible).

• Performance Status: ECOG performance status 0-1. Measurable Disease: At least one measurable lesion per RECIST 1.1 criteria. 4. Prior Immunotherapy:

Patients who have received PD-1, PD-L1, PD-L2, or CTLA-4 inhibitors, or other therapies targeting T-cell co-stimulation/checkpoint pathways:

Must have achieved complete response (CR), partial response (PR), or stable disease (SD) ≥6 months during treatment.

Only one prior immunotherapy regimen is allowed (e.g., neoadjuvant and adjuvant regimens using the same immunotherapy are considered one regimen).

Switching to a different immunotherapy regimen for non-immunotherapy-related progression is permissible if cumulative SD duration ≥6 months.

• Organ Function:

Hematology:

ANC ≥1.5×10⁹/L, PLT ≥75×10⁹/L, Hb ≥90 g/L. No blood product transfusion or growth factor support (e.g., G-CSF, EPO) within 2 weeks prior to screening.

Hepatology:

TBIL ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤5×ULN if liver metastases present).

Renal Function:

Serum Cr ≤1.5×ULN or CrCl >60 mL/min.

Thyroid Function:

TSH, FT4, FT3 within CTC AE Grade 0-1. 7. Survival Expectancy: ≥3 months. 8. Informed Consent: Voluntary participation and signed written informed consent.

Exclusion criteria

• Known severe hypersensitivity (≥Grade 3) to any monoclonal/polyclonal antibody, chidamide, or anlotinib components.
• Necrotic lesions identified within 4 weeks prior to enrollment, with investigator-judged risk of major bleeding.
• Chemotherapy, targeted therapy, or immunomodulatory agents (including thymosin, interferon, IL-2, etc.) within 2 weeks prior to enrollment.

Washout period determined by clinical resolution of adverse events (AEs) and prior treatment regimens.

• Palliative radiotherapy to localized lesions within 4 weeks prior to enrollment, unless the lesion is non-target and other measurable target lesions exist.
• Grade ≥3 irAEs during prior immunotherapy.
• Prior treatment with HDAC inhibitors or anti-angiogenic agents.
• Urine protein ≥2+ or 24-hour urinary protein ≥1 g.
• Systolic BP >140 mmHg or diastolic BP >90 mmHg despite treatment.
• Persistent toxicity from prior antitumor therapy (per NCI CTCAE v5.0) >Grade 1, excluding: alopecia, Grade 2 fatigue, Grade 2 anemia, or asymptomatic lab abnormalities.
• Symptomatic CNS metastases (e.g., edema, steroid requirement) or leptomeningeal disease.
• Systemic immunosuppressive drugs (excluding topical/inhaled corticosteroids or physiological doses ≤10 mg/day prednisone equivalent) or corticosteroids for contrast allergy within 4 weeks prior to enrollment.
• Active autoimmune diseases (e.g., interstitial pneumonia, colitis, thyroiditis) or history of severe autoimmune conditions requiring systemic therapy.

Exceptions: Vitiligo, childhood asthma (resolved without treatment), or mild asthma managed without bronchodilators.

• Ongoing anti-tuberculosis therapy or treatment within 1 year prior to screening.
• Conditions requiring long-term immunosuppressive therapy or systemic corticosteroids at immunosuppressive doses.
• Severe Cardiac Disease or Significant Cardiac Symptoms.
• Other Circumstances Deemed Unsuitable by the Investigator