Back to resultsMAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
Primary Purpose
Urothelial Carcinoma, Head and Neck Cancer, Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A10, Immuno-oncology, Metastatic, Urothelial Cancer, Previously Treated, T Cell Receptor, Inoperable, Advanced, Cancer, Bladder, Head and neck, Melanoma
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 following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
- Subject is HLA-A*02:01 and/or HLA-A*02:06 positive.
- Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
- Subject meets disease-specific requirements per protocol
- Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
- Subject's tumor shows positive MAGE-A10 expression
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Subject has a left ventricular ejection fraction ≥50%.
- Subject is fit for leukapheresis and has adequate venous access for the cell collection.
- Female subject of childbearing potential (FCBP) must have a negative urine or serum pregnancy test or male subject must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter.
- Subject must have adequate organ function per protocol
Exclusion Criteria:
- Subject is HLA-A*02:05 in either allele, HLA-B*15:01 and/or HLA-B*46:01 positive. Subject has any A*02 null allele (designated with an "N", e.g. A*02:32N) as the sole HLA-A*02 allele.
- Subject has received or plans to receive excluded therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy per protocol
- Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment
- Subject has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
- Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
- Subject has an electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with bundle branch block [BBB]) over 3 consecutive ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.
- Subject has symptomatic CNS metastases.
- Subject has a history of chronic or recurrent severe autoimmune or immune mediated disease
- 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.
Sites / Locations
- Massachusetts General Hospital
- Washington University - School of Medicine
- Roswell Park Cancer Institute
- Ohio State University Wexner Medical Center
- Fox Chase Cancer Center
- Tennessee Oncology - Sarah Cannon Research Institute
- Vanderbilt - Ingram Cancer Center
- MD Anderson Cancer Center
- Princess Margaret Cancer Centre
- Start Madrid-FJD, Fundación Jimѐnez Díaz
- Hospital Universitario 12 Octubre Avda. de Córdoba
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Arm Description
Outcomes
Primary Outcome Measures
Number of subjects with adverse events (AE), including serious adverse events (SAE).
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.
Evaluation of the persistence of genetically modified T cells
Evaluation of the persistence of the infused T cells in the periphery.
Measurement of RCL in genetically modified T cells.
Evaluation of RCL in Subject PBMCs using PCR-based assay.
Assessment of dose limiting toxicities to determine optimally tolerated dose range
Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0
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 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
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02989064
Brief Title
MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
Official Title
Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
October 2016 (Actual)
Primary Completion Date
December 18, 2019 (Actual)
Study Completion Date
June 4, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adaptimmune
4. Oversight
5. Study Description
Brief Summary
This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose.
The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer.
Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma, Head and Neck Cancer, Melanoma, Bladder Urothelial Carcinoma
Keywords
Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A10, Immuno-oncology, Metastatic, Urothelial Cancer, Previously Treated, T Cell Receptor, Inoperable, Advanced, Cancer, Bladder, Head and neck, Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Intervention Description
Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1
Primary Outcome Measure Information:
Title
Number of subjects with adverse events (AE), including serious adverse events (SAE).
Description
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.
Time Frame
3 years
Title
Evaluation of the persistence of genetically modified T cells
Description
Evaluation of the persistence of the infused T cells in the periphery.
Time Frame
3 years
Title
Measurement of RCL in genetically modified T cells.
Description
Evaluation of RCL in Subject PBMCs using PCR-based assay.
Time Frame
3 years
Title
Assessment of dose limiting toxicities to determine optimally tolerated dose range
Description
Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0
Time Frame
3 years
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 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 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 years
Title
Interval between the date of first documented evidence of 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 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 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 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)
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 following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
Subject is HLA-A*02:01 and/or HLA-A*02:06 positive.
Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
Subject meets disease-specific requirements per protocol
Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
Subject's tumor shows positive MAGE-A10 expression
Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Subject has a left ventricular ejection fraction ≥50%.
Subject is fit for leukapheresis and has adequate venous access for the cell collection.
Female subject of childbearing potential (FCBP) must have a negative urine or serum pregnancy test or male subject must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter.
Subject must have adequate organ function per protocol
Exclusion Criteria:
Subject is HLA-A*02:05 in either allele, HLA-B*15:01 and/or HLA-B*46:01 positive. Subject has any A*02 null allele (designated with an "N", e.g. A*02:32N) as the sole HLA-A*02 allele.
Subject has received or plans to receive excluded therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy per protocol
Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment
Subject has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
Subject has an electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with bundle branch block [BBB]) over 3 consecutive ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.
Subject has symptomatic CNS metastases.
Subject has a history of chronic or recurrent severe autoimmune or immune mediated disease
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.
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
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
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
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
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
Vanderbilt - Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD 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
Facility Name
Start Madrid-FJD, Fundación Jimѐnez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario 12 Octubre Avda. de Córdoba
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
35372008
Citation
Hong DS, Butler MO, Pachynski RK, Sullivan R, Kebriaei P, Boross-Harmer S, Ghobadi A, Frigault MJ, Dumbrava EE, Sauer A, Brophy F, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou DG, Wang R, Solis LM, Duose DY, Sanderson JP, Gerry AB, Marks D, Bai J, Norry E, Fracasso PM. Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. Front Oncol. 2022 Mar 18;12:818679. doi: 10.3389/fonc.2022.818679. eCollection 2022.
Results Reference
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MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
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