clinical study of chidamide combined with toripalimab in the treatment of advanced melanoma

Conditions: Melanoma

Summary: the study was a single-arm study designed to evaluate the efficacy and safety of chidamide combined with toripalimab.


Eligibility criteria:
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.