Esophageal Cancer, Esophagogastric Junction Cancer
Conditions
Keywords
Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A4, Immuno-oncology, Metastatic, Esophagogastric Junction, Esophageal Cancer
Brief summary
This study will investigate the efficacy of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and tumor antigen status and whose esophageal or esophagogastric junction (EGJ) cancer expresses the MAGE-A4 protein.
Interventions
Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1
Sponsors
ICON plc
Adaptimmune
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥18 and \<75 years * Diagnosis of Esophageal cancer or Esophagogastric junction cancer. * Previously received treatment for advanced or metastatic disease. * Measurable disease according to RECIST v1.1. * HLA-A\*02 positive * Tumor shows MAGE-A4 expression confirmed by central laboratory. * ECOG Performance Status of 0 or1. * Left ventricular ejection fraction (LVEF) ≥50%. Note: other protocol defined Inclusion criteria may apply Key
Exclusion criteria
1. Positive for any HLA-A\*02 allele other than: one of the inclusion alleles 2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study 3. Active autoimmune or immune mediated disease 4. Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases 5. Other prior malignancy that is not considered by the Investigator to be in complete remission. Clinically significant cardiovascular disease 6. Uncontrolled intercurrent illness 7. Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus 8. Pregnant or breastfeeding Note: other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by Independent Radiological Assessment Committee (IRAC) | From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion). | Confirmed tumor response (complete response \[CR\] or partial response \[PR\]) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by IRAC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | From start of lymphodepleting chemotherapy to end of Interventional Phase (up to 5 months) | An AE was defined as any untoward medical occurrence in a subject or clinical study participant temporally associated with the use of the study intervention, whether or not considered related to the study intervention. Therefore, an AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants with AEs (including SAEs), SAEs and AESI including cytokine release syndrome, ICANS, and prolonged cytopenia are presented. |
| Time to Response (TTR) by IRAC | From T-cell infusion until first documented confirmed CR or PR | TTR (CR or PR) was defined as the interval between the date of first T-cell infusion and the earliest date of first documented confirmed CR or confirmed PR. |
| Duration of Response (DoR) by IRAC | From initial date of first confirmed response (CR or PR) until PD or death | DoR is defined as duration between the initial date of the confirmed complete or partial response to the date of progressive disease or death, where tumor response and disease progression were assessed by IRAC. |
| Best Overall Response (BOR) by IRAC | From T-cell infusion until disease progression | BOR is the best response recorded from the start of T-cell infusion until disease progression as assessed by IRAC. Response categories are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD). |
| Progression Free Survival (PFS) by IRAC | From T-cell infusion until first documented PD, as assessed by IRAC, or death due to any cause, whichever occurs first | PFS is defined as time from the T-cell infusion to the date of the first documentation of progressive disease (PD) as assessed by IRAC or death due to any cause, whichever occurs first. |
| Overall Response Rate (ORR) by Investigator Assessment | From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion). | Confirmed tumor response (complete response \[CR\] or partial response \[PR\]) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator Assessment |
| Time to Response (TTR) by Investigator Assessment | From T-cell infusion until first documented confirmed CR or PR | TTR (CR or PR) was defined as the interval between the date of first T-cell infusion and the earliest date of first documented confirmed CR or confirmed PR |
| Best Overall Response (BOR) by Investigator Assessment | From T-cell infusion until disease progression (Up to 5 months) | BOR is the best response recorded from the start of T-cell infusion until disease progression as assessed by the Investigator. Response categories are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD). |
| Progression Free Survival (PFS) by Investigator Assessment | From T-cell infusion until first documented PD, as assessed by Investigator, or death due to any cause, whichever occurs first (up to 5 months) | PFS is defined as the time from the T-cell infusion to the date of the first documentation of progressive disease (PD) as assessed by investigator assessment or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | From T-cell infusion to death due to any reason (up to 7 months) | OS is defined as the time from the date of first T-cell infusion to the date of death (due to any cause). |
| Replication Competent Lentivirus | From T-cell infusion to end study (up to 7 months) | The presence of RCL was assessed by qPCR targeting a segment of the vesicular stomatitis virus glycoprotein (VSV G) coding sequence. 1 participant had at least 1 post-infusion sample tested for RCL. The count of participants with RCL post-infusion is presented. |
| Insertional Oncogenesis (IO) | From 1 year post T-cell infusion | Deoxyribonucleic acid (DNA) from participants peripheral blood mononuclear cell (PBMC) samples are subjected to lentiviral vector integration site analysis by next-generation sequencing, thus evaluating both the clonality status of the transduced cell population and the genomic localization of individual integration sites. The outcome measure is the number of participants with integration sites representing more than 5% of all unique sites. |
| Peak Persistence | From T-cell infusion to end study (up to 7 months) | Peak persistence of ADP-A2M4CD8 cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC). |
| Time to Peak Persistence | From T-cell infusion to end study (up to 7 months) | Time from ADP-A2M4CD8 T-cell infusion to peak persistence of cells. |
| Concordance of the MAGE A-4 Clinical Trial Assay and in Vitro Diagnostic (IVD) Kit. | Screening visit | Concordance of the MAGE A-4 clinical trial assay and in vitro diagnostic (IVD) kit. |
| Duration of Response (DoR) by Investigator Assessment | From initial date of first confirmed response (CR or PR) until PD or death | DoR is defined as duration between the initial date of the confirmed complete or partial response to the date of progressive disease or death, where tumor response and disease progression were assessed by Investigator Assessment. |
Countries
Canada, Spain, United States
Participant flow
Recruitment details
This was a Phase 2 open-label, single treatment, clinical trial of ADP-A2M4CD8 in participants with advanced esophageal or esophagogastric junction cancers
Pre-assignment details
All participants were assigned to one treatment (ADP-A2M4CD8)
Participants by arm
| Arm | Count |
|---|---|
| Esophageal Eligible participants with esophageal cancer who received ADP-A2M4CD8 as a single infusion | 2 |
| Esophagogastric Junction Eligible participants with esophagogastric junction cancer who received ADP-A2M4CD8 as a single infusion | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
Baseline characteristics
| Characteristic | Esophageal | Esophagogastric Junction | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 68 years | 72 years | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 1 / 1 |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 1 / 2 | 1 / 1 |
Outcome results
Primary
Overall Response Rate (ORR) by Independent Radiological Assessment Committee (IRAC)
Confirmed tumor response (complete response \[CR\] or partial response \[PR\]) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by IRAC
Time frame: From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion).
Population: Participants who received ADP-A2M4CD8. No subject images were assessed by Independent Reviewer due to lack of efficacy observed on Investigator review. Thus, no results are reported.
Secondary
Best Overall Response (BOR) by Investigator Assessment
BOR is the best response recorded from the start of T-cell infusion until disease progression as assessed by the Investigator. Response categories are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD).
Time frame: From T-cell infusion until disease progression (Up to 5 months)
Population: Participants who received ADP-A2M4CD8.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Esophageal | Best Overall Response (BOR) by Investigator Assessment | Complete Response | 0 Participants |
| Esophageal | Best Overall Response (BOR) by Investigator Assessment | Partial Response | 0 Participants |
| Esophageal | Best Overall Response (BOR) by Investigator Assessment | Stable Disease | 2 Participants |
| Esophageal | Best Overall Response (BOR) by Investigator Assessment | Progressive Disease | 0 Participants |
| Esophagogastric Junction | Best Overall Response (BOR) by Investigator Assessment | Progressive Disease | 0 Participants |
| Esophagogastric Junction | Best Overall Response (BOR) by Investigator Assessment | Complete Response | 0 Participants |
| Esophagogastric Junction | Best Overall Response (BOR) by Investigator Assessment | Stable Disease | 1 Participants |
| Esophagogastric Junction | Best Overall Response (BOR) by Investigator Assessment | Partial Response | 0 Participants |
Secondary
Best Overall Response (BOR) by IRAC
BOR is the best response recorded from the start of T-cell infusion until disease progression as assessed by IRAC. Response categories are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD).
Time frame: From T-cell infusion until disease progression
Population: Participants who received ADP-A2M4CD8. No subject images were assessed by Independent Reviewer due to lack of efficacy observed on Investigator review. Thus, no results are reported.
Secondary
Concordance of the MAGE A-4 Clinical Trial Assay and in Vitro Diagnostic (IVD) Kit.
Concordance of the MAGE A-4 clinical trial assay and in vitro diagnostic (IVD) kit.
Time frame: Screening visit
Population: Due to study termination, an IVD kit for companion diagnosis was not developed. Thus, there is no data to report regarding concordance of the MAGE A-4 clinical trial assay and the IVD companion diagnostic kit.
Secondary
Duration of Response (DoR) by Investigator Assessment
DoR is defined as duration between the initial date of the confirmed complete or partial response to the date of progressive disease or death, where tumor response and disease progression were assessed by Investigator Assessment.
Time frame: From initial date of first confirmed response (CR or PR) until PD or death
Population: Participants who received ADP-A2M4CD8 and had a confirmed CR or PR. No subjects had a confirmed CR or PR. Thus, DoR was not calculated, and no results are reported.
Secondary
Duration of Response (DoR) by IRAC
DoR is defined as duration between the initial date of the confirmed complete or partial response to the date of progressive disease or death, where tumor response and disease progression were assessed by IRAC.
Time frame: From initial date of first confirmed response (CR or PR) until PD or death
Population: Participants who received ADP-A2M4CD8 and had a confirmed CR or PR. No subjects had a confirmed CR or PR. Thus, no results are reported.
Secondary
Insertional Oncogenesis (IO)
Deoxyribonucleic acid (DNA) from participants peripheral blood mononuclear cell (PBMC) samples are subjected to lentiviral vector integration site analysis by next-generation sequencing, thus evaluating both the clonality status of the transduced cell population and the genomic localization of individual integration sites. The outcome measure is the number of participants with integration sites representing more than 5% of all unique sites.
Time frame: From 1 year post T-cell infusion
Population: Participants who received ADP-A2M4CD8 and had a sample analyzed for IO. All subjects died prior to 1 year post T-cell infusion, subsequently no samples were obtained or analyzed.
Secondary
Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI)
An AE was defined as any untoward medical occurrence in a subject or clinical study participant temporally associated with the use of the study intervention, whether or not considered related to the study intervention. Therefore, an AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants with AEs (including SAEs), SAEs and AESI including cytokine release syndrome, ICANS, and prolonged cytopenia are presented.
Time frame: From start of lymphodepleting chemotherapy to end of Interventional Phase (up to 5 months)
Population: Participants who received ADP-A2M4CD8
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Esophageal | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | SAE | 1 Participants |
| Esophageal | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI- ICANS | 0 Participants |
| Esophageal | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI - cytokine release syndrome | 1 Participants |
| Esophageal | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI- Prolonged cytopenia | 0 Participants |
| Esophageal | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AE | 2 Participants |
| Esophagogastric Junction | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI- Prolonged cytopenia | 1 Participants |
| Esophagogastric Junction | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AE | 1 Participants |
| Esophagogastric Junction | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | SAE | 1 Participants |
| Esophagogastric Junction | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI - cytokine release syndrome | 1 Participants |
| Esophagogastric Junction | Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) | AESI- ICANS | 0 Participants |
Secondary
Overall Response Rate (ORR) by Investigator Assessment
Confirmed tumor response (complete response \[CR\] or partial response \[PR\]) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator Assessment
Time frame: From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion).
Population: Participants who received ADP-A2M4CD8.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esophageal | Overall Response Rate (ORR) by Investigator Assessment | 0 Participants |
| Esophagogastric Junction | Overall Response Rate (ORR) by Investigator Assessment | 0 Participants |
Secondary
Overall Survival (OS)
OS is defined as the time from the date of first T-cell infusion to the date of death (due to any cause).
Time frame: From T-cell infusion to death due to any reason (up to 7 months)
Population: Participants who received ADP-A2M4CD8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Esophageal | Overall Survival (OS) | 19.64 Weeks |
| Esophagogastric Junction | Overall Survival (OS) | 29.71 Weeks |
Secondary
Peak Persistence
Peak persistence of ADP-A2M4CD8 cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC).
Time frame: From T-cell infusion to end study (up to 7 months)
Population: Participants who received ADP-A2M4CD8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Esophageal | Peak Persistence | 59546.3 copies/microgram DNA |
| Esophagogastric Junction | Peak Persistence | 135581.5 copies/microgram DNA |
Secondary
Progression Free Survival (PFS) by Investigator Assessment
PFS is defined as the time from the T-cell infusion to the date of the first documentation of progressive disease (PD) as assessed by investigator assessment or death due to any cause, whichever occurs first.
Time frame: From T-cell infusion until first documented PD, as assessed by Investigator, or death due to any cause, whichever occurs first (up to 5 months)
Population: Participants who received ADP-A2M4CD8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Esophageal | Progression Free Survival (PFS) by Investigator Assessment | 14.43 Weeks |
| Esophagogastric Junction | Progression Free Survival (PFS) by Investigator Assessment | 8.43 Weeks |
Secondary
Progression Free Survival (PFS) by IRAC
PFS is defined as time from the T-cell infusion to the date of the first documentation of progressive disease (PD) as assessed by IRAC or death due to any cause, whichever occurs first.
Time frame: From T-cell infusion until first documented PD, as assessed by IRAC, or death due to any cause, whichever occurs first
Population: Participants who received ADP-A2M4CD8. No subject images were assessed by IRAC due to lack of efficacy observed on Investigator review. Hence, no results are reported.
Secondary
Replication Competent Lentivirus
The presence of RCL was assessed by qPCR targeting a segment of the vesicular stomatitis virus glycoprotein (VSV G) coding sequence. 1 participant had at least 1 post-infusion sample tested for RCL. The count of participants with RCL post-infusion is presented.
Time frame: From T-cell infusion to end study (up to 7 months)
Population: Participants who received ADP-A2M4CD8 and had a post-infusion sample tested for VSV-G
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esophageal | Replication Competent Lentivirus | 0 Participants |
| Esophagogastric Junction | Replication Competent Lentivirus | 0 Participants |
Secondary
Time to Peak Persistence
Time from ADP-A2M4CD8 T-cell infusion to peak persistence of cells.
Time frame: From T-cell infusion to end study (up to 7 months)
Population: Participants who received ADP-A2M4CD8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Esophageal | Time to Peak Persistence | 11.5 Days |
| Esophagogastric Junction | Time to Peak Persistence | 17 Days |
Secondary
Time to Response (TTR) by Investigator Assessment
TTR (CR or PR) was defined as the interval between the date of first T-cell infusion and the earliest date of first documented confirmed CR or confirmed PR
Time frame: From T-cell infusion until first documented confirmed CR or PR
Population: Participants who received ADP-A2M4CD8 and had a confirmed CR or PR. No subjects had a confirmed CR or PR. Thus, TTR was not calculated, and no results are reported.
Secondary
Time to Response (TTR) by IRAC
TTR (CR or PR) was defined as the interval between the date of first T-cell infusion and the earliest date of first documented confirmed CR or confirmed PR.
Time frame: From T-cell infusion until first documented confirmed CR or PR
Population: Participants who received ADP-A2M4CD8 and had a confirmed CR or PR. No subjects had a confirmed CR or PR. Thus, no results are reported.