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

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

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

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Chidamide combined with Toripalimab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chidamide combined with Toripalimab<br> | Drug: Chidamide combined with Toripalimab<br>* chidamide：oral, 30 mg/time, twice weekly; Toripalimab：intravenous drip, 240mg, once every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR)as measure of efficacy by RECIST 1.1 | Up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free survival （PFS） | Defined as the time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first) | Up to approximately 24 months | 
| Overall Survival（OS） | OS as measure of efficacy by RECIST 1.1 | Up to approximately 24 months | 
| Duration of Response(DoR) | DoR as measure of efficacy by RECIST 1.1 | Up to approximately 24 months | 
| Disease control rate（DCR） | Defined as the percentage of patients who have achieved a confirmed response of at least CR or PR or a response of SD | Up to approximately 24 months | 
| Incidence Rate of each Toxicity (safety and tolerability) | safety and tolerability as measure of efficacy by CTCAE 5.0 | Up to approximately 24 months |