ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2)
- Conditions
- Esophagogastric Junction CancerEsophageal Cancer
- Interventions
- Genetic: Autologous genetically modified ADP-A2M4CD8 cells
- Registration Number
- NCT04752358
- Lead Sponsor
- Adaptimmune
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- 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
- Positive for any HLA-A*02 allele other than: one of the inclusion alleles
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study
- Active autoimmune or immune mediated disease
- Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases
- Other prior malignancy that is not considered by the Investigator to be in complete remission. Clinically significant cardiovascular disease
- Uncontrolled intercurrent illness
- Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
- Pregnant or breastfeeding
Note: other protocol defined Inclusion/Exclusion criteria may apply.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous genetically modified ADP-A2M4CD8 cells Autologous genetically modified ADP-A2M4CD8 cells -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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.
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.
Trial Locations
- Locations (17)
University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
University Of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Washington University School of Medicine- Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence Cancer Institute Franz Clinic
🇺🇸Portland, Oregon, United States
University Of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
McGill University Health Centre Glen Site
🇨🇦Montreal, Quebec, Canada
Hospital Clinico Universitario de Valencia
🇪🇸Ibáñez, Valencia, Spain
Hospital Universitari Vall d'Hebron
🇪🇸la Vall d'Hebron, Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Córdoba, Madrid, Spain
Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Navarro, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Madrid Sanchinarro (CIOCC)
🇪🇸Madrid, Spain
City of Hope National Medical Center
🇺🇸Duarte, California, United States