Description:
This first time in human study is intended for men and women at least 18 years of age who
have advanced lung cancer which has grown or returned after being treated. In particular, it
is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and
a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose
escalation trial that will evaluate 3 doses of transduced cells administered after a
lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .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 receive lymphodepleting
chemotherapy with cyclophosphamide and fludarabine, followed by the 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 lung cancer. The study will evaluate three
different cell dose levels in order to find out the target cell dose. Once the target cell
dose is determined, additional subjects will be enrolled to further test the safety and
effects at this cell dose.
Subjects will be seen frequently by the Study Physician right after receiving their T cells
back and up to first 6 months. After that, subjects will be seen every three months. Subjects
will be seen every 6 months by their Study Physician for the first 5 years after the T cell
infusion. If the T cells are found in the blood at five years, then the subjects will
continue to be seen once a year until the T cells are no longer found in the blood for a
maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the
subject will be contacted by the Study Physician for the next 10 years. Subjects who have a
confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose
tumor continues to express the appropriate antigen target may be eligible for a second
infusion. All subjects, completing or withdrawing from the Interventional Phase of the study,
will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All
subjects will continue to be followed for overall survival during the long-term follow-up
phase.
Title
- Brief Title: MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC
- Official Title: A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
Clinical Trial IDs
- ORG STUDY ID:
ADP 0022-003
- NCT ID:
NCT02592577
Conditions
- Non-Small Cell Lung Cancer
- Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T | | Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T |
Purpose
This first time in human study is intended for men and women at least 18 years of age who
have advanced lung cancer which has grown or returned after being treated. In particular, it
is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and
a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose
escalation trial that will evaluate 3 doses of transduced cells administered after a
lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .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 receive lymphodepleting
chemotherapy with cyclophosphamide and fludarabine, followed by the 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 lung cancer. The study will evaluate three
different cell dose levels in order to find out the target cell dose. Once the target cell
dose is determined, additional subjects will be enrolled to further test the safety and
effects at this cell dose.
Subjects will be seen frequently by the Study Physician right after receiving their T cells
back and up to first 6 months. After that, subjects will be seen every three months. Subjects
will be seen every 6 months by their Study Physician for the first 5 years after the T cell
infusion. If the T cells are found in the blood at five years, then the subjects will
continue to be seen once a year until the T cells are no longer found in the blood for a
maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the
subject will be contacted by the Study Physician for the next 10 years. Subjects who have a
confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose
tumor continues to express the appropriate antigen target may be eligible for a second
infusion. All subjects, completing or withdrawing from the Interventional Phase of the study,
will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All
subjects will continue to be followed for overall survival during the long-term follow-up
phase.
Trial Arms
Name | Type | Description | Interventions |
---|
Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T | Experimental | | - Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T
|
Eligibility Criteria
Key Inclusion Criteria:
1. Subject has histologically or cytologically confirmed diagnosis of advanced non-small
cell lung cancer (stage IIIB or IV) or recurrent disease
2. Subject has received at least one line of prior therapy
3. Subjects with known epidermal growth factor receptor (EGFR) mutations or anaplastic
lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed
(progressive disease or unacceptable toxicity) at least one prior EGFR or ALK or ROS1
tyrosine kinase inhibitor, respectively. Subject may have received PD-1 or PDL-1
inhibitors and or chemotherapy. There is no limit on lines of prior anti-cancer
therapy (a washout period applies for recent anti-cancer treatments).
4. Subject has measurable disease according to RECIST v1.1 criteria prior to
lymphodepletion.
5. Subject is HLA-A*02:01 or HLA-A*02:06 positive.
6. Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is
unavailable) has been pathologically reviewed by a designated central laboratory
confirming MAGE-A10 expression.
7. Subject has an ECOG Performance Status 0-1 and anticipated life expectancy >6 months
prior to apheresis and >3 months prior to lymphodepletion.
8. Subject is ≥18 to ≤75 years of age
9. Adequate organ function
Key Exclusion Criteria:
1. Subject is HLA-A*02:05, HLA-B*15:01 and/or HLA-B*46:01 positive.
2. History of chronic or recurrent (within the last year prior to enrollment) severe
autoimmune or active immune-mediated disease requiring steroids or other
immunosuppressive treatments.
3. Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS
metastasis must have received treatment and be neurologically stable for at least 1
month prior to leukapheresis and lymphodepletion.
4. Active malignancy besides NSCLC within 3 years prior to screening.
5. Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection;
- Clinically significant cardiac disease
- Inadequate pulmonary function
- Interstitial lung disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; cardiac and pulmonary assessments, including ECG and troponin. |
Secondary Outcome Measures
Measure: | Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1 |
Measure: | Interval between the date of first T cell infusion dose and first documented evidence of CR or PR |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of time to first response |
Measure: | Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of duration of response |
Measure: | Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of duration of stable disease |
Measure: | Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of progression-free survival |
Measure: | Interval between the date of first T cell infusion and date of disease progression or death due to any cause |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Evaluation of the efficacy of the treatment by assessment of overall survival |
Measure: | Best Overall Response (BOR) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Best Overall Response (BOR), defined as the best response recorded from the date of T cell infusion until disease progression |
Measure: | To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion. |
Time Frame: | 15 years |
Safety Issue: | |
Description: | Presence of any of the following LTFU AEs:
New malignancies
New incidence or exacerbation of a pre-existing neurologic disorder
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder
New incidence of a hematologic disorder
Opportunistic and/or serious infections
Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy Persistence of MAGE-A10c796T and replication-competent lentivirus (RCL) over time. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Adaptimmune |
Trial Keywords
- Previously Treated
- Cell Therapy
- T Cell Therapy
- MAGE-A10
- Immuno-oncology
- T Cell Receptor
- Metastatic
Last Updated
April 9, 2021