MAGE-A4ᶜ¹º³²T for Multi-Tumor
Study Details
Study Description
Brief Summary
This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
|
Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1
|
| Experimental: Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
|
Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Up to 10 subjects will be considered for Radiation sub-study. Radiation with an intensity of 1.4Gy for 5 days before infusion of MAGE-A4c1032T cells
|
Outcome Measures
Primary Outcome Measures
- Number of subjects with adverse events (AE), including serious adverse events (SAEs). [3.5 years]
Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.
- Determining dose limiting toxicities (DLT) and optimally tolerated dose range [3.5 years]
Evaluate DLTs and toxicity assessment using NCI CTCAE.
- Evaluation of persistence of genetically modified T cells. [3.5 years]
Evaluation of persistence of genetically modified T cells in the periphery.
- Measurement of RCL in genetically modified T cells. [3.5 years]
Evaluation of RCL in subject PBMCs using PCR-based assay.
Secondary Outcome Measures
- Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [3.5 years]
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
- Interval between the date of first T cell infusion dose and first documented evidence of CR or PR. [3.5 years]
Evaluation of the efficacy of the treatment by assessment of time to first response.
- Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause. [3.5 years]
Evaluation of the efficacy of the treatment by assessment of duration of response.
- Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause. [3.5 years]
Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
- Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause [3.5 years]
Evaluation of the efficacy of the treatment by assessment of progression-free survival.
- Interval between the date of first T cell infusion and date of death due to any cause. [3.5 years]
Evaluation of the efficacy of the treatment by assessment of overall survival.
- Number and % of subjects having any Long Term Follow Up Adverse Events (AEs) [15 years post last treatment (infusion)]
New occurrence of any malignancy New occurrence or exacerbation of a pre-existing neurologic disorder New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder New occurrence of a hematologic disorder New occurrence of any opportunistic and/or serious infections New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy
Other Outcome Measures
- MAGE-A4c1032T cell trafficking in tumor lesion(s). [3.5 years]
Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject is ≥18 to 75 years of age at the time of signing the study informed consent.
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Subject has histologically confirmed diagnosis of any one of the indicated tumor types
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Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
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Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
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Adequate organ function as indicated in the study protocol
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Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
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Subject meets disease-specific requirements per protocol
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Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
Exclusion Criteria:
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Subject does not express appropriate HLA-A genotype
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Subject is receiving excluded therapy/treatment per protocol
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Subject has symptomatic CNS metastases.
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Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
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Subject has active infection with HIV, HBV, HCV or HTLV
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Subject is pregnant or breastfeeding.
Additional Exclusion Criteria for the Radiation Substudy:
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Subject does not meet eligibility criteria for the main study (ADP-0044-001).
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Subject does not have at least one target lesion amenable to radiation.
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Certain radiation therapy within 6 months of clinical trial are an exclusion.
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Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Miami | Miami | Florida | United States | 33136 |
| 2 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 3 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 4 | Washington University | Saint Louis | Missouri | United States | 63112 |
| 5 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 6 | Duke University Medical Center, Duke Cancer Institute | Durham | North Carolina | United States | 27710 |
| 7 | Ohio State University Wexner Medical Center | Columbus | Ohio | United States | 43210 |
| 8 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 9 | Tennessee Oncology - Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 10 | M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 11 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G1X6 |
Sponsors and Collaborators
- Adaptimmune
Investigators
- Principal Investigator: David Hong, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ADP-0044-001