SURPASS-2 study
Research type
Research Study
Full title
A Phase 2 Open-Label Clinical Trial of ADP-A2M4CD8 in Subjects with Advanced Esophageal or Esophagogastric Junction Cancers
IRAS ID
298740
Contact name
Jeff Evans
Contact email
Sponsor organisation
Adaptimmune LLC
Eudract number
2020-005802-24
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
IND, 18950
Duration of Study in the UK
6 years, 10 months, 1 days
Research summary
Research Summary: Adaptimmune are looking for new and better ways to treat advanced oesophageal or gastroesophageal junction (GEJ) cancers. Many patients present with advanced disease, where only 5% survive up to 5-years and with only a median survival of 8 to 10 months. Given the very low survival rates in oesophageal and gastric cancer, there is a high degree of unmet need.
A protein called MAGE-A4 is highly overexpressed in tumours of multiple cancers, which makes it a promising target for oncotherapy.
Adaptimmunes’ investigational medicinal product, ADP-A2M4CD8 is made up of patients changed T-cells. These T-cells are taken from participants tumours who express MAGE-4. The T-cells are genetically modified in a laboratory and are re-introduced to the participants via infusion into their bloodstream to attack the cancer cells. These T-cells, once taken from the participants’ own blood and modified is considered an Investigational drug. The study drug has a specifically high affinity/attraction to the MAGE-A4 protein in oesophageal and GEJ cancers. The purpose of this study is to find how well the study drug works in attacking the participants advanced cancer and to see how safe it is.
About 45 people aged 18 years or older in North America, Europe (EU) and the United Kingdom (UK) are expected to take part in this study.
Participation is voluntary and the study will be explained via the patient information sheet and discussion with Study Doctor. Eligible patients who consent to participate will have the following; a leukapheresis procedure to collect T-cells; 4 days of chemotherapy with cyclophosphamide and fludarabine pre-study drug infusion and one intravenous infusion of the study drug. Patients will remain on the study until they meet one of the criteria for discontinuation or if they withdraw. They will be in the follow-up phase of this study for a maximum of 15 years.Lay summary of study results: Sponsor: Adaptimmune LLC General information about the clinical trial:
The study was planned to take place in USA, Canada Spain, UK, and France. Participants were enrolled in Spain and USA only.
The study was conducted from October 2021 to June 2023.
The main aim of the study was to see how well the ADP-A2M4CD8, a T-cell therapy, works in treating Esophageal or Esophagogastic junction cancer (GEJ). This was measured by tracking the size of the tumors. The study was closed early after the recruitment of three participants due to recruitment difficulties. In this case, having a small number of participants makes it hard to see whether the ADP A2M4CD8 was having any effect..
Population of trial participants:
It was planned to enroll forty-five advanced esophageal or esophagogastric junction cancer participants into the study. In fact, only three participants were enrolled and received study drug prior to the study closing.
All three participants were white males. The median age was 69 years. Two participants had esophageal cancer and 1 participant had esophagogastric junction cancer.
Which medicines were studied?:
The study drug tested was ADP-A2M4CD8. ADP-A2M4CD8 was made using T-cells from each participant.
What were the side effects?:
All three participants experienced side effects with vomiting being the most common (all participants had this) followed by cytokine release syndrome (CRS), shortness of breath, decreases in some types of white blood cells, feeling sick and fever (66.7% participants had each of these side effects). CRS is a group of symptoms caused by release of chemicals from cells after the changed T cells are given to a participant.
Two participants had serious side effects. One participant had respiratory failure and the other participant had fever, CRS, and bleeding in the oesophagus. The CRS was considered by the Investigator to be related to the participant receiving ADP-A2M4CD8 All other side effects were considered by the Investigator to be not related to the participant receiving ADP-A2M4CD8. All these side effects resolved.
All three participants had side effects related to ADP-A2M4CD8. Overall, the most frequently occurring side effect related to ADP-A2M4CD8 was CRS (2 participants, 66.7%). One participant had CRS (onset on Day 4 with a duration of 14 days; considered not serious) and the other participant had CRS (onset on Day 2 with a duration of 8 days; considered serious). Both participants received tocilizumab as treatment for CRS and all events of CRS resolved.
No participants experienced ICANS (immune effector cell-associated neurotoxicity). ICANS is a condition of the brain that affects thinking and consciousness that can be serious or life threatening.
No participants experienced prolonged cytopenias, which is a shortage of all blood cells including Lay Language Results Summary
Product: ADP-A2M4CD8
Study: SURPASS-2
Based on Clinical Study Report (06 May 2024) Date:05 September 2024 Lay Language Results Summary: Version 1.0 Page 3 of 3 white blood cells, red blood cells and platelets. These are known side effects associated with T-cell therapies.
All three participants died due to the disease under study (1 participant died during the Interventional Phase and 2 participants died during Long Term Follow Up (LFTU)). All deaths occurred more than 30 days after ADP-A2M4CD8 were given to the participant.
No side effects were reported during LTFU.
What were the overall results of the study?:
ADP-A2M4CD8 T-cell infusion with prior administration of fludarabine and cyclophosphamide lymphodepleting chemotherapy had an acceptable safety profile in participants with esophageal or GEJ cancers. No on-study deaths were related to the T-cell infusion. All CRS events got better with treatment. . No participants experienced ICANS or prolonged cytopenia. The CRS events were low severity, occurred soon after T-cell infusion, and resolved. Tocilizumab, was used to treat the events of CRS. In the LTFU phase, there were no side effects reported.. None of the patients had a decrease in the size of their tumors after receiving ADP-A2M4CD8. The best response seen was no change in the size of the tumor (i.e., it didn’t get bigger or smaller)”.
How has this study helped patients and researchers?
Experience has been gathered in the treatment of these types of patients with this disease and the new information about the safety of ADP-A2M4CD8 in these patients has been recorded and will be taken into consideration in further studies.REC name
London - West London & GTAC Research Ethics Committee
REC reference
21/LO/0706
Date of REC Opinion
27 Jan 2022
REC opinion
Further Information Favourable Opinion