Back to resultsMAGE-A4ᶜ¹º³²T for Multi-Tumor
Primary Purpose
Urinary Bladder Cancer, Melanoma, Head and Neck Cancer
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Sponsored by
About this trial
This is an interventional treatment trial for Urinary Bladder Cancer focused on measuring Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A4, Immuno-oncology, Metastatic, Urothelial Cancer, Previously Treated, T Cell Receptor, Squamous, adenosquamous, adenocarcinoma or large cell NSCLC, Squamous or adenocarcinoma esophageal cancer, Sarcoma, Melanoma, Bladder, Ovarian, Radiation therapy
Eligibility Criteria
Inclusion Criteria:
- Subject is ≥18 to 75 years of age at the time of signing the study informed consent.
- Subject has histologically confirmed diagnosis of any one of the indicated tumor types
- Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
- Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
- Adequate organ function as indicated in the study protocol
- Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
- Subject meets disease-specific requirements per protocol
7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
Exclusion Criteria:
- Subject does not express appropriate HLA-A genotype
- Subject is receiving excluded therapy/treatment per protocol
- Subject has symptomatic CNS metastases.
- Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
- Subject has active infection with HIV, HBV, HCV or HTLV
- Subject is pregnant or breastfeeding.
Additional Exclusion Criteria for the Radiation Substudy:
- Subject does not meet eligibility criteria for the main study (ADP-0044-001).
- Subject does not have at least one target lesion amenable to radiation.
- Certain radiation therapy within 6 months of clinical trial are an exclusion.
- Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
Sites / Locations
- University of Miami
- Moffitt Cancer Center
- Washington University School of Medicine
- Washington University
- Roswell Park Cancer Institute
- Duke University Medical Center, Duke Cancer Institute
- Ohio State University Wexner Medical Center
- Fox Chase Cancer Center
- Tennessee Oncology - Sarah Cannon Research Institute
- M.D. Anderson Cancer Center
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
Arm Description
Outcomes
Primary Outcome Measures
Number of subjects with adverse events (AE), including serious adverse events (SAEs).
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
Evaluate DLTs and toxicity assessment using NCI CTCAE.
Evaluation of persistence of genetically modified T cells.
Evaluation of persistence of genetically modified T cells in the periphery.
Measurement of RCL in genetically modified T cells.
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).
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.
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.
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.
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
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.
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)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03132922
Brief Title
MAGE-A4ᶜ¹º³²T for Multi-Tumor
Official Title
Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 15, 2017 (Actual)
Primary Completion Date
September 2032 (Anticipated)
Study Completion Date
September 2035 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adaptimmune
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Bladder Cancer, Melanoma, Head and Neck Cancer, Ovarian Cancer, Non-Small Cell Lung Cancer, Esophageal Cancer, Gastric Cancer, Synovial Sarcoma, Myxoid Round Cell Liposarcoma, Gastroesophageal Junction
Keywords
Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A4, Immuno-oncology, Metastatic, Urothelial Cancer, Previously Treated, T Cell Receptor, Squamous, adenosquamous, adenocarcinoma or large cell NSCLC, Squamous or adenocarcinoma esophageal cancer, Sarcoma, Melanoma, Bladder, Ovarian, Radiation therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Arm Type
Experimental
Arm Title
Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Intervention Description
Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1
Intervention Type
Radiation
Intervention Name(s)
Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of subjects with adverse events (AE), including serious adverse events (SAEs).
Description
Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.
Time Frame
3.5 years
Title
Determining dose limiting toxicities (DLT) and optimally tolerated dose range
Description
Evaluate DLTs and toxicity assessment using NCI CTCAE.
Time Frame
3.5 years
Title
Evaluation of persistence of genetically modified T cells.
Description
Evaluation of persistence of genetically modified T cells in the periphery.
Time Frame
3.5 years
Title
Measurement of RCL in genetically modified T cells.
Description
Evaluation of RCL in subject PBMCs using PCR-based assay.
Time Frame
3.5 years
Secondary Outcome Measure Information:
Title
Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
Description
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
Time Frame
3.5 years
Title
Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
Description
Evaluation of the efficacy of the treatment by assessment of time to first response.
Time Frame
3.5 years
Title
Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
Description
Evaluation of the efficacy of the treatment by assessment of duration of response.
Time Frame
3.5 years
Title
Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.
Description
Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
Time Frame
3.5 years
Title
Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause
Description
Evaluation of the efficacy of the treatment by assessment of progression-free survival.
Time Frame
3.5 years
Title
Interval between the date of first T cell infusion and date of death due to any cause.
Description
Evaluation of the efficacy of the treatment by assessment of overall survival.
Time Frame
3.5 years
Title
Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
Description
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
Time Frame
15 years post last treatment (infusion)
Other Pre-specified Outcome Measures:
Title
MAGE-A4c1032T cell trafficking in tumor lesion(s).
Description
Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions
Time Frame
3.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is ≥18 to 75 years of age at the time of signing the study informed consent.
Subject has histologically confirmed diagnosis of any one of the indicated tumor types
Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
Adequate organ function as indicated in the study protocol
Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
Subject meets disease-specific requirements per protocol
7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
Exclusion Criteria:
Subject does not express appropriate HLA-A genotype
Subject is receiving excluded therapy/treatment per protocol
Subject has symptomatic CNS metastases.
Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
Subject has active infection with HIV, HBV, HCV or HTLV
Subject is pregnant or breastfeeding.
Additional Exclusion Criteria for the Radiation Substudy:
Subject does not meet eligibility criteria for the main study (ADP-0044-001).
Subject does not have at least one target lesion amenable to radiation.
Certain radiation therapy within 6 months of clinical trial are an exclusion.
Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Hong, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63112
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Duke University Medical Center, Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Tennessee Oncology - Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X6
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
32002290
Citation
Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.
Results Reference
derived
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MAGE-A4ᶜ¹º³²T for Multi-Tumor
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