A Study of Toripalimab or Combining With Temozolomide（iv） in the Treatment of Advanced/Metastatic Malignant Melanoma

Study Overview
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Brief Summary
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This study evaluate toripalimab or combining with temozolomide for injection in the treatment of advanced/metastatic malignant melanoma. Participants in arm A receive toripalimab, in arm B receive toripalimab plus temozolomide

Official Title
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An Exploratory Study of PD-1 Antibody(Toripalimab) or Combining With Temozolomide for Injection in the Treatment of Advanced/Metastatic Malignant Melanoma

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Drug: toripalimab
* Drug: Temozolomide Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Confirmed pathologic or cytologic diagnosis of advanced/metastatic malignant melanomawithout BRAF V600E mutation ECOG PS 0-1; Age :18  75 years old; There were measurable lesions according to RECIST 1.1 and the lesions that had been irradiated showed definite progression after radiotherapy and the lesion was considered measurable only if it was not the only lesion Proper function of the cardiovascular system, liver, kidney and bone marrow ; Subject with at most one systemic therapy for advanced/metastatic malignant melanoma Survival is expected to exceed 3 months The subjects showing good compliance voluntarily participated in the study and signed the informed consent Exclusion Criteria: •Previously treated with TMZ, PD-1, or PD-L1; Complicated with other malignant tumors; Subjects with central nervous system metastases and/or cancerous meningitis;(Unless the subjects are asymptomatic or have been treated , no radiographic evidence of new BMs or BMs enlargement is found at least 2 weeks after BMs treatment.If the subjects have active or new untreated asymptomatic central nervous system (CNS) metastases found on imaging during the screening phase,they must receive radiotherapy Uncontrolled pleural effusion ,pericardial effusion or ascites requiring repeated drainage Received major surgical treatment or significant traumatic injury within Random 28 days prior Severe arterial/venous thrombosis events，Such as cerebrovascular accident (including temporary ischemic attack) ,deep vein thrombosis and pulmonary embolismwithin Random 6 months prior Subjects with a history of psychotropic substance abuse and being unable to get rid of it or with mental disorders Subjects with any severe and/or uncontrolled disease,including : Subjects with poor blood pressure control (systolic≥ 150 mmHg or diastolic ≤100mmHg) Subjects with myocardial ischemia or myocardial infarction or arrhythmia above grade I (including male QTC ≥450ms(male) and female QTC ≥470ms) And ≥grade 2 congestive heart failure (New York Heart Association (NYHA)) Active or uncontrolled severe infection (≥CTC AE grade 2 infection) liver cirrhosis,active hepatitis*;*active hepatitis(Hepatitis B reference: HBsAg positive, and HBV DNA test value exceeds the normal valueHepatitis C reference: HCV antibody positive, and HCV virus titer detection value exceeds the upper limit of normal value HIV infected Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L) urine protein≥++,andConfirmated 24-hour urinary protein quantification>1.0 g Subjects received a preventive vaccineor attenuated vaccine within 4 weeks prior to first administration Participated in other clinical trials within 4 weeks Active autoimmune disease（Such as the following, but not limited to: autoimmune hepatitis interstitial pneumonia enteritis vasculitis, nephritis。Subjects with asthma requiring bronchodilators for medical intervention were not included） requiring systemic treatment（Such as the use of palliative drugs, corticosteroids, or immunosuppressants） occurred within 2 years prior to initial administration.Alternative therapy(Examples include thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy Other conditions that investigators consider the patients are not suitable

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>toripalimab 3mg/kg, Q2w; | Drug: toripalimab<br>* toripalimab 3mg/kg, Q2w;<br>* Other names: triprizumab;|
| Experimental: Arm B<br>toripalimab 3mg/kg, Q2w; Temozolomide 150mg/m2,d1-5,Q4w | Drug: toripalimab<br>* toripalimab 3mg/kg, Q2w;<br>* Other names: triprizumab;Drug: Temozolomide Injection<br>* Temozolomide 150mg/m2,d1-5,Q4w<br>* Other names: Temoda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | overall survival | 3 years | 
| PFS | Progression free survival | 1 years | 
| DCR | Disease contral rate | 8 weeks | 
| 1-year PFS | progression free survival at 1 year (1year PFS) rate | 1 year after treatment initiation | 
| 6-month PFS | progression free survival at 6 months (6-month PFS) rate | 6 months after treatment initiation | 
| 1-year OS | overall survival at 1 year (1 year OS) rate | 1 year after treatment initiation | 
| 2-year OS | overall survival at 2 years (2 year OS) rate | 2 year after treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malignant melanoma, PD-1 antibody, temozolomide for injection, toripalimab