Malignant Melanoma
Conditions
Keywords
HLA-A2, gp100
Brief summary
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
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.
Interventions
BIOLOGICALGPA-TriMAR-T
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.
Sponsors
The Second Affiliated Hospital of Hainan Medical University
Hainan Cancer Hospital
Timmune Biotech Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities; 2. All subjects must be able to comply with all the scheduled procedures in the study; 3. HLA\_A2 genotype and gp100 positive malignant melanoma： Ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy; 4. At least one measurable lesion per RECIST V1.1; 5. Aged 18 to 69 years; 6. Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2; 7. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 8. All other treatment induced adverse events must have been resolved to ≤grade 1; 9. 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
1. 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); 2. 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; 3. Lactating women or women of childbearing age who plan to conceive during the time period; 4. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); 5. Known history of infection with HIV; 6. Subjects need systematic usage of corticosteroid; 7. Subjects need systematic usage of immunosuppressive drug; 8. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 9. Other reasons the investigator consider the patient may not be suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03） | 24 months | Incidence of treatment-related adverse events as assessed by CTCAE v4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate[CR] （Complete response rate per the revised International Working Group (IWG) Response Criteria） | 24 months | Complete response rate per the revised International Working Group (IWG) Response Criteria |
| Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria） | 24 months | Partial response rate per the revised International Working Group (IWG) Response Criteria |
| Duration of Response （The time from response to relapse or progression） | 24 months | The time from response to relapse or progression |
| Progression Free Survival （The time from the first day of treatment to the date on which disease progresses.） | 24 months | The time from the first day of treatment to the date on which disease progresses. |
| Overall Survival （The number of patient alive, with or without signs of cancer） | 24 months | The number of patient alive, with or without signs of cancer |
Countries
China
Contacts
Primary ContactHaifeng Lin
Backup ContactBin Gao
Outcome results
None listed