ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2)

A Phase 2 Open-Label Clinical Trial of ADP-A2M4CD8 in Subjects With Advanced Esophageal or Esophagogastric Junction Cancers

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.

Study Overview

• Status: Terminated
• Conditions: Esophageal Cancer; Esophagogastric Junction Cancer
• Intervention / Treatment: Genetic: Autologous genetically modified ADP-A2M4CD8 cells

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre Glen Site
• Spain
  • Madrid, Spain, 228040
    • Hospital Fundación Jiménez Díaz
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro (CIOCC)
  • Navarro, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Barcelona
    • la Vall d'Hebron, Barcelona, Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Madrid
    • Córdoba, Madrid, Spain, 28041
      • Hospital Universitario 12 de Octubre
  • Valencia
    • Ibáñez, Valencia, Spain, 46010
      • Hospital Clínico Universitario de Valencia
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine- Siteman Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous genetically modified ADP-A2M4CD8 cells	Genetic: Autologous genetically modified ADP-A2M4CD8 cells; Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From start of lymphodepleting chemotherapy to end of Interventional Phase (up to 5 months)
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.	From T-cell infusion until first documented confirmed CR or PR
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.	From initial date of first confirmed response (CR or PR) until PD or death
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).	From T-cell infusion until disease progression
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.	From T-cell infusion until first documented PD, as assessed by IRAC, or death due to any cause, whichever occurs first
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	From T-cell infusion to end of Interventional Phase (Up to 5 months from T-cell infusion).
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	From T-cell infusion until first documented confirmed CR or PR
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.	From initial date of first confirmed response (CR or PR) until PD or death
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).	From T-cell infusion until disease progression (Up to 5 months)
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.	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)
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).	From T-cell infusion to death due to any reason (up to 7 months)
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.	From T-cell infusion to end study (up to 7 months)
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.	From 1 year post T-cell infusion
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).	From T-cell infusion to end study (up to 7 months)
Time to Peak Persistence	Time from ADP-A2M4CD8 T-cell infusion to peak persistence of cells.	From T-cell infusion to end study (up to 7 months)
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.	Screening visit

Collaborators and Investigators

• Sponsor: Adaptimmune
• Collaborators: ICON plc

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): June 9, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Cell Therapy; Metastatic; Esophageal Cancer; Immuno-oncology; T Cell Therapy; SPEAR T Cell; MAGE-A4; Esophagogastric Junction
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: ADP-0055-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No