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

Early Phase 1

• Conditions: Malignant Melanoma
• Interventions: Biological: GPA-TriMAR-T

• Registration Number: NCT03649529
• Lead Sponsor: Timmune Biotech Inc.

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.

Study Timeline

• Study First Submitted: 2018-08-23
• Study First Submitted QC: 2018-08-26
• Study First Posted: 2018-08-28
• Study Start: 2018-09-27
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-05
• Last Update Posted: 2019-12-06
• Primary Completion: 2021-09-15
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GPA-TriMAR-T	GPA-TriMAR-T	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (2)

Hainan Cancer Hospital; 🇨🇳 Haikou, Hainan, China

The Second Affiliated Hospital of Hainan Medical University; 🇨🇳 Haikou, Hainan, China