NCT04752358

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

Terminated Phase 2 Results posted Last updated 4 September 2024

What this trial tests

Phase 2 trial testing Autologous genetically modified ADP-A2M4CD8 cells in Esophageal Cancer in 3 participants. Terminated before completion.

Timeline

15 September 2021

Primary endpoint
9 June 2023

15 December 2023

Quick facts

Lead sponsor	Adaptimmune
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3
Start date	15 September 2021
Primary completion	9 June 2023
Estimated completion	15 December 2023
Sites	17 locations across Canada, United States, Spain

Drugs / interventions tested

• Autologous genetically modified ADP-A2M4CD8 cells

Conditions studied

• Esophageal Cancer — all drugs for Esophageal Cancer →
• Esophagogastric Junction Cancer — all drugs for Esophagogastric Junction Cancer →

Sponsor

Adaptimmune — full company profile →

Who can join

Adults 18 to 75, any sex, with Esophageal Cancer or Esophagogastric Junction Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number and Percentage of Participants With Adverse Events (AEs) Including Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESI) Secondary · 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.

AE

Group	Value	95% CI
Esophageal	2
Esophagogastric Junction	1

SAE

Group	Value	95% CI
Esophageal	1
Esophagogastric Junction	1

AESI - cytokine release syndrome

Group	Value	95% CI
Esophageal	1
Esophagogastric Junction	1

AESI- ICANS

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

AESI- Prolonged cytopenia

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	1

Overall Response Rate (ORR) by Investigator Assessment Secondary · 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

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

Best Overall Response (BOR) by Investigator Assessment Secondary · 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).

Complete Response

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

Partial Response

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

Stable Disease

Group	Value	95% CI
Esophageal	2
Esophagogastric Junction	1

Progressive Disease

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

Progression Free Survival (PFS) by Investigator Assessment Secondary · 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.

Group	Value	95% CI
Esophageal	14.43	8.14 – 20.71
Esophagogastric Junction	8.43	8.43 – 8.43

Overall Survival (OS) Secondary · 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).

Group	Value	95% CI
Esophageal	19.64	18.57 – 20.71
Esophagogastric Junction	29.71	29.71 – 29.71

Replication Competent Lentivirus Secondary · 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.

Group	Value	95% CI
Esophageal	0
Esophagogastric Junction	0

Peak Persistence Secondary · 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).

Group	Value	95% CI
Esophageal	59546.3	41432.7 – 77660
Esophagogastric Junction	135581.5	135581.5 – 135581.5

Time to Peak Persistence Secondary · From T-cell infusion to end study (up to 7 months)

Time from ADP-A2M4CD8 T-cell infusion to peak persistence of cells.

Group	Value	95% CI
Esophageal	11.5	8 – 15
Esophagogastric Junction	17	17 – 17

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events were collected from the start of lymphodepleting chemotherapy until the end of the interventional phase (up to 5 months). Deaths were collected from start of lymphodepletion chemotherapy until the end of the study (up to 7 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Esophageal

Serious: 1/2 (50%)

Deaths: 2/2

Esophagogastric Junction

Serious: 1/1 (100%)

Deaths: 1/1

Serious adverse events (4 terms)

Reaction	System	Esophageal	Esophagogastric Junction
Cytokine release syndrome	Immune system disorders	—	—
Oesophageal haemorrhage	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (32 terms — click to expand)

Reaction	System	Esophageal	Esophagogastric Junction
Vomiting	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Haematemesis	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Asthenia	General disorders	—	—
Fatigue	General disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
White blood cell count decreased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Migraine with aura	Nervous system disorders	—	—
Sciatica	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Insomnia	Psychiatric disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Bronchial hyperreactivity	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Cytokine release syndrome	Immune system disorders	—	—
Cytomegalovirus infection reactivation	Infections and infestations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Cytokine release syndrome, Oesophageal haemorrhage, Pyrexia, Respiratory Failure.

Data from ClinicalTrials.gov NCT04752358 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Autologous T cell therapy for MAGE-A4⁺ solid cancers in HLA-A*02⁺ patients: a phase 1 trial.
   Hong DS, Van Tine BA, Biswas S, McAlpine C, et al · · 2023 · cited 159× · PMID 36624315 · DOI 10.1038/s41591-022-02128-z
2. Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer.
   Nin DS, Deng LW. · · 2023 · cited 45× · PMID 36980267 · DOI 10.3390/cells12060926
3. Cancer/testis antigens: promising immunotherapy targets for digestive tract cancers.
   Ai H, Yang H, Li L, Ma J, et al · · 2023 · cited 18× · PMID 37398650 · DOI 10.3389/fimmu.2023.1190883
4. Enhancing Efficacy of TCR-engineered CD4 + T Cells Via Coexpression of CD8α.
   Anderson VE, Brilha SS, Weber AM, Pachnio A, et al · · 2023 · cited 11× · PMID 36826388 · DOI 10.1097/cji.0000000000000456
5. Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer.
   Naik A, Lattab B, Qasem H, Decock J. · · 2024 · cited 10× · PMID 38596293 · DOI 10.1016/j.omton.2024.200768
6. Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation.
   O'Neill JR, Yébenes Mayordomo M, Mitulović G, Al Shboul S, et al · · 2024 · cited 8× · PMID 38604503 · DOI 10.1016/j.mcpro.2024.100764
7. Melanoma-associated antigen A4: A cancer/testis antigen as a target for adoptive T-cell receptor T-cell therapy.
   Knafler G, Ho AL, Moore KN, Pollack SM, et al · · 2025 · cited 6× · PMID 39970827 · DOI 10.1016/j.ctrv.2025.102891
8. Transforming Cancer Diagnostics: The Emergence of Liquid Biopsy and Epigenetic Markers.
   Saha D, Kanjilal P, Kaur M, Menon SV, et al · · 2025 · cited 4× · PMID 40959208 · DOI 10.1002/mco2.70388