Clinical Study of Chidamide Combined With Toripalimab in the Treatment of Advanced Melanoma

Clinical Study of Chidamide Combined With Toripalimab in the Treatment of Advanced Melanoma

The study was a single-arm study designed to evaluate the efficacy and safety of Chidamide combined with Toripalimab.

Inclusion Criteria:

• aged ≥ 18 years, male or female
• histologically and/or cytologically confirmed melanoma, clinically diagnosed as inoperable stage III-IV
• previous treatment for advanced tumors (including chemotherapy, targeted, anti-vascular drugs, etc.) failure or no standard treatment, and no PD- (L) 1/CTLA-4 drug treatment; if neoadjuvant/adjuvant therapy has received PD- (L) 1/CTLA-4 drug treatment, the total duration of drug treatment should be ≥6 months
• if there is brain metastasis, local treatment must have been received before participating in this study and clinical stability ≥ 3 months
• ECOG score 0-1
• at least one measurable lesion (according to RECISTv1.1 evaluation criteria)
• absolute neutrophil count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L
• other organ function needs to meet: ① cardiac function needs to meet: left ventricular ejection fraction ≥ 50%, no organic arrhythmia; ② liver function needs to meet: ALT and AST ≤ 2.5 times the upper limit of normal (such as with liver metastasis, ALT and AST ≤ 5 times the upper limit of normal), total bilirubin ≤ 1.5 times the upper limit of normal;③ renal function needs to meet: creatinine ≤ 1.5 times the upper limit of normal; ④ coagulation function: international normalized ratio (International Normalized Ratio,INR) ≤ 1.5 times upper limit of normal; prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5 times upper limit of normal (unless the subject was receiving anticoagulant therapy and PT and APTT were within the expected range of anticoagulant therapy at screening); ⑤ Thyroid function: thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were within ± 10% of normal values.
• Expected survival time ≥ 3 months
• Voluntarily participate in this clinical trial and sign a written informed consent.
• Previous anti-tumor therapy (chemotherapy, radiotherapy, targeting, traditional Chinese medicine, other immunotherapy) requires eluting for 28 days.
• The adverse effects of previous antitumor therapy were resolved to grade 0-1 before the screening period (as determined by NCI CTCAE 5.0; Except for toxicity, such as hair loss, which the investigator determined did not pose a safety risk to the subject)

Exclusion Criteria:

• no measurable lesions, such as pleural or pericardial exudates, ascites, etc.
• choroidal melanoma
• previous treatment with HDAC inhibitors (including cedaramide, romidepsin, vorinostat, bellistat, panobinostat, etc.)
• history of interstitial lung disease or pneumonia requiring oral or intravenous steroids
• previous vaccination or planned vaccination with live vaccines (seasonal influenza vaccine without live vaccines is allowed), major surgery within 30 days before the first study treatment
• active infection [active bacterial, viral, fungal, mycobacterial, parasitic infections or other infections (excluding fungal infections of the nail bed) within 4 weeks before the screening period, or any major infection event requiring intravenous antibiotic therapy, or targeted antiviral therapy, or hospitalization; Active hepatitis is defined as HBsAg positive with HBV DNA≥500 IU/ml or HCV antibody positive with HCV copy number > the upper limit of normal], or persistent fever within 14 days before screening
• history of immunodeficiency, including positive HIV testing, or other acquired, congenital immunodeficiency diseases, or history of organ transplantation
• uncontrolled cardiovascular disease; history of clinically significant QT prolongation, or screening period > 470 ms for females and > 450 ms for males
• positive baseline pregnancy test in female subjects who are pregnant or lactating or fertile females; or subjects of childbearing age who are unwilling to take effective contraceptive measures for at least 180 days during study participation and after the last dose of study drug
• According to the investigator 's judgment, there are concomitant diseases that seriously jeopardize the subject' s safety or affect the subject 's completion of the study (e.g., severe hypertension ≥ 180/110 mmHg, uncontrolled diabetes, thyroid disease, Hypertriglyceridemia ≥ grade 2, etc.)
• History of definite neurological or psychiatric disorders, including epilepsy or dementia
• Any condition that, in the opinion of the investigator, would make participation in this study inappropriate.