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

Malignant Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03649529
• Other study ID #: T2018-7
• Status: Recruiting
• Phase: Early Phase 1
• Start date: September 27, 2018
• Est. completion date: January 1, 2022

Study information

• Verified date: December 2019
• Source: Timmune Biotech Inc.
• Contact: Haifeng Lin
• Phone: +86 13322060949
• Email: 13322060949[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: January 1, 2022
• Est. primary completion date: September 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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: ? 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.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Biological:
• GPA-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.

Locations

Country	Name	City	State
China	Hainan Cancer Hospital	Haikou	Hainan
China	The Second Affiliated Hospital of Hainan Medical University	Haikou	Hainan

Sponsors (3)

Lead Sponsor	Collaborator
Timmune Biotech Inc.	Hainan Cancer Hospital, The Second Affiliated Hospital of Hainan Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19. Review. — View Citation

Zhang G, Liu R, Zhu X, Wang L, Ma J, Han H, Wang X, Zhang G, He W, Wang W, Liu C, Li S, Sun M, Gao B. Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol. 2013 Nov-Dec;91(10):615-24. doi: 10.1038/icb.2013.45. Epub 2013 Oct 8. — View Citation

Zhang G, Wang L, Cui H, Wang X, Zhang G, Ma J, Han H, He W, Wang W, Zhao Y, Liu C, Sun M, Gao B. Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Sci Rep. 2014 Jan 6;4:3571. doi: 10.1038/srep03571. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Duration of Response (The time from response to relapse or progression)	The time from response to relapse or progression	24 months
Secondary	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
Secondary	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