Malignant MelanomaEarly Phase 1NCT03649529
Treatment of Malignant Melanoma With GPA-TriMAR-T Cell Therapy
A Early Phase 1 study testing GPA-TriMAR-T in people with Malignant Melanoma, run by Timmune Biotech Inc. at 2 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- GPA-TriMAR-T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesChina
- Study dates
- 27 Sep 2018to 1 Jan 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 9Show fewer
- 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);
Who cannot join
- 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;
Show all 9Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Hainan Cancer Hospital
Haikou, Hainan, 570100
Yuyang Tian, +86 18686853849, tianyuyang@163.com
- Recruiting
The Second Affiliated Hospital of Hainan Medical University
Haikou, Hainan, 570100
Haifeng Lin, +86 13322060949, 13322060949@163.com
Yasong Wu, +86 18020091931, yasong.wu@timmune.com
About this study
Official title: Adoptive Immunotherapy for HLA_A2 Genotype gp100 Positive Malignant Melanoma With GPA-TriMAR-T Cell
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.
Read the 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.
- Conditions
- Malignant Melanoma
- Being tested
- GPA-TriMAR-T
- Keywords
- HLA-A2, gp100
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GPA-TriMAR-TBiological
Also called TCR-mimic-CAR-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.
| Study group | Role | What they receive |
|---|---|---|
| GPA-TriMAR-T | Experimental | 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. Receives: Biological: GPA-TriMAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 months
Secondary outcomes (5)
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
Measured: 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
Measured: 24 months
Duration of Response (The time from response to relapse or progression)
The time from response to relapse or progression
Measured: 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.
Measured: 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
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start27 Sep 2018
- Primary completion15 Sep 2021 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Timmune Biotech Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Second Affiliated Hospital of Hainan Medical University, Hainan Cancer Hospital
- Responsible party
- Sponsor
- Investigators
- Haifeng Lin, Principal investigator, The Second Affiliated Hospital of Hainan Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03649529
- Sponsor's protocol ID
- T2018-7
- Status last verified
- Dec 2019
- First submitted
- 23 Aug 2018
- Last updated
- 6 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24389689Zhang 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.
PubMed 24100387Neelapu 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.
PubMed 28925994
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Immunotherapy for HLA_A2 Genotype gp100 Positive Malignant Melanoma With GPA-TriMAR-T Cell
- ClinicalTrials.gov ID
- NCT03649529
- Acronym / sponsor ID
- T2018-7
- Conditions
- Malignant Melanoma
- Keywords
- HLA-A2, gp100
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Timmune Biotech Inc.Industry (pharma, biotech, devices)
- Collaborators
- The Second Affiliated Hospital of Hainan Medical University, Hainan Cancer Hospital
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 15 Sep 2021 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 28 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| GPA-TriMAR-T | Experimental | Biological: GPA-TriMAR-TPatients' 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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GPA-TriMAR-TAlso: TCR-mimic-CAR-TPatients 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. | Biological | GPA-TriMAR-T |
Primary outcome
safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03)
Time frame: 24 months
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
5 secondary outcomes
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria)
Time frame: 24 months
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria)
Time frame: 24 months
Duration of Response (The time from response to relapse or progression)
Time frame: 24 months
Progression Free Survival (The time from the first day of treatment to the date on which disease progresses.)
Time frame: 24 months
Overall Survival (The number of patient alive, with or without signs of cancer)
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2019.
- Background: PubMed 24389689Zhang 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.
- Background: PubMed 24100387Zhang 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.
- Background: PubMed 28925994Neelapu 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.
- Individual participant dataSharing planned: No
Related trials for Malignant Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Haifeng Lin principal investigator
The Second Affiliated Hospital of Hainan Medical University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing GPA-TriMAR-T in people with Malignant Melanoma, run by Timmune Biotech Inc. at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Haifeng Lin (+86 13322060949, 13322060949@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.03) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03649529, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2019.