Treatment of Malignant Melanoma With GPA-TriMAR-T Cell Therapy

Study Overview
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Brief Summary
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Malignant melanoma have been reported to be characterized with high gp100 expression. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the GPA-TriMAR-T cells will recognize and kill target cells that express gp100(209-217) peptides in the form MHC-I complex, thus eliminating malignant melanoma from the body.

Detailed Description
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GPA-TriMAR is a modified chimeric antigen receptor (CAR) that consist of three subunit in it's outer membrane domain. The outer membrane domain linked to the inner membrane 4-1BB/CD3ζ domain through the transmembrane domain, thus compose the complete chimeric antigen receptor. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the modified GPA-TriMAR-T cells will recognize and kill malignant melanoma cells in the body, and in the meanwhile the other two subunits function to stimulate the innate immune system and enhance GPA-TriMAR-T cells tumor Infiltration.

Official Title
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Adoptive Immunotherapy for HLA_A2 Genotype gp100 Positive Malignant Melanoma With GPA-TriMAR-T Cell

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Biological: GPA-TriMAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must personally sign and date the consent form before initiating any study specific procedures or activities; All subjects must be able to comply with all the scheduled procedures in the study; HLA_A2 genotype and gp100 positive malignant melanoma： Ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy; At least one measurable lesion per RECIST V1.1; Aged 18 to 69 years; Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2; Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; All other treatment induced adverse events must have been resolved to ≤grade 1; Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome); Exclusion Criteria: Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment); Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator; Lactating women or women of childbearing age who plan to conceive during the time period; Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); Known history of infection with HIV; Subjects need systematic usage of corticosteroid; Subjects need systematic usage of immunosuppressive drug; Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; Other reasons the investigator consider the patient may not be suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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
Interventional Model Description: Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells,and then infused back into the patient.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GPA-TriMAR-T<br>Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells, and these cells will then be infused back into the patient for intervention. | Biological: GPA-TriMAR-T<br>* Patients will undergo leukapheresis to isolate autologous T cells, these T cells will be activated and modified to express GPA-TriMAR in the manufacture facility, and eventually infused back into the body for treatment.<br>* Other names: TCR-mimic-CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03） | Incidence of treatment-related adverse events as assessed by CTCAE v4.03 | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate[CR] （Complete response rate per the revised International Working Group (IWG) Response Criteria） | Complete response rate per the revised International Working Group (IWG) Response Criteria | 24 months | 
| Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria） | Partial response rate per the revised International Working Group (IWG) Response Criteria | 24 months | 
| Duration of Response （The time from response to relapse or progression） | The time from response to relapse or progression | 24 months | 
| Progression Free Survival （The time from the first day of treatment to the date on which disease progresses.） | The time from the first day of treatment to the date on which disease progresses. | 24 months | 
| Overall Survival （The number of patient alive, with or without signs of cancer） | The number of patient alive, with or without signs of cancer | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HLA-A2, gp100