Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer

Inclusion Criteria:

1. Signed Informed Consent Form (ICF).

2. Patients must have histologically confirmed diagnosis of metastatic, recurrent orpersistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma ofthe cervix which is not amenable to curative treatment with surgery and/or radiationtherapy.

3. Age ≥ 18 years and ≤ 70 years.

4. Patients must have measurable disease per RECIST v1.1; measurable lesions aredefined as those that can be accurately measured in at least one dimension (longestdiameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magneticresonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within apreviously irradiated field will be designated as "non-target" lesions unlessprogression is documented or a biopsy is obtained to confirm persistence at least 90days following completion of radiation therapy.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Life expectancy exceeds 3 months.

7. Patients must have progressed on at least one line of platinum-based systemictherapy. Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimenfor management of recurrent, persistent or metastatic cervical cancer. However,adjuvant chemotherapy could be counted as one prior regimen in patients who hadrecurrence during or within 6 months of completion of therapy.

8. Patients must have adequate organ function as defined by the following criteria:

• Absolute neutrophil count (ANC) (≥ 1.5×10^9/L), hemoglobin of ≥ 90 g/L,platelets ≥ 80 ×10^9/L

• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 ×ULN may be enrolled)

• Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)

• Baseline albumin ≥ 28 g/L

• Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with freeTriiodothyronine [FT3] or free Thyroxine [FT4] levels ≤ 1 × ULN may beenrolled)

Exclusion Criteria:

1. Prior exposure to immune checkpoint inhibitors, including but not limited to otheranti-PD-1 and anti-PD-L1 antibodies, or prior exposure to HDAC inhibitors.

2. Any condition requiring systemic treatment with corticosteroids (>10 mg dailyprednisone or equivalents) or other immunosuppressive medications within 14 daysbefore first dose of study drug. Corticosteroids for topical use, nasal spray, andinhaled steroids are allowed.

3. Active autoimmune diseases that require systemic treatment. Alternative treatments (such as thyroxine, insulin, or physiological corticosteroids for adrenal orpituitary insufficiency) are permitted.

4. Clinically significant cardiovascular diseases, including but not limited tocongestive heart failure (New York heart association [NYHA] class > 2), unstable orsevere angina, severe acute myocardial infarction within 1 year before enrollment,supraventricular or ventricular arrhythmia which need medical intervention, or QTinterval male ≥ 450 ms, female ≥ 470 ms.

5. Arterial or venous thrombosis within 6 months before enrollment

6. Uncontrolled hypertension defined as systolic pressure ≥ 160 mmHg and/or diastolicpressure ≥ 100 mmHg despite antihypertensive drugs.

7. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.

8. Coagulation abnormalities (INR > 2.0, PT > 16s), with bleeding tendency or arereceiving thrombolytic or anticoagulant therapy.

9. Has known active central nervous system metastases.

10. Patients had a diagnosed and/or treated additional malignancy within the last 5years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinomaof the skin, or in situ cervical cancer that has undergone potentially curativetherapy.

11. Has a known history of immunodeficiency including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.

12. Has known active Hepatitis B or Hepatitis C.