dm+d

Unassigned

New Medicines

Oesophageal cancer and oesophagogastric junction cancer, MAGE-A4-positive

Information

New molecular entity
Adaptimmune
Adaptimmune

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials

Category

A genetically modified autologous melanoma-associated antigen 4 (MAGE A4) specific T cell therapy, with cells that also express the CD8α co-receptor alongside the engineered TCR that targets MAGE-A4. Preclinical data indicate that co-expression of CD8α may broaden the immune response against solid tumors and increase anti-tumour activity by leveraging CD4+ cells into CD8+ killer or cytotoxic T‑cells while retaining their CD4+ helper function. Given as a single dose.
Gastro-oesophageal junction (GOJ) cancer describes cancers where the centre of the tumour is less than 5cm above or below where the oesophagus meets the stomach. It is more common in men than women, with 13.6 new cases for every 100,000 males and 7.2 for every 100,000 females in UK in 2015 [1]. For oesophageal cancer, there were 19.7 new cases for every 100,000 males and 8.5 for every 100,000 females in UK in 2016-2018 [2].
Oesophageal cancer and oesophagogastric junction cancer, MAGE-A4-positive
Intravenous infusion

Trial or other data

Sep 21PII SURPASS-2 trial to assess the efficacy of ADP-A2M4CD8 in patients who have the appropriate human leukocyte antigen (HLA) and tumour antigen status and whose oesophageal or oesophagogastric junction cancer expresses the MAGE-A4 protein starts (NCT04752358; ADP-0055-002). The open-label trial intends to enrol 45 patients in the US, Canada, France, Spain and the UK (sites include The Christie NHS Foundation Trust, Beatson West of Scotland Cancer Centre, University College Hospital, and Guys and St Thomas NHS Foundation Trust). Primary outcome is overall response rate at 2.5 years; collection of these data is due to complete Apr 23 [3].
Aug 21Top-line results from PI SURPASS trial at data cut-off of Aug 21, showed that majority of the patients with solid tumours experienced antitumour activity with a disease control rate of 86%. The overall response rate (ORR) was 36%, in 22 evaluable patients of the 25 treated population. ADP-A2M4CD8 cell therapy showed improved tumour cell killing and engagement of the broader immune system to fight cancer. Confirmed complete response (CR) (n = 1, 4.5%) was observed for ovarian cancer (which remained ongoing at 6 months post-infusion), while confirmed partial responses (PR; n = 7, 31.8%) were seen in ovarian (n = 2), head and neck (n = 3), esophagogastric junction (n = 1), bladder, and synovial sarcoma cancers. Stable disease (SD; n = 11, 50%) was seen in ovarian cancer (n = 3), EGJ (n = 2), oesophageal cancer (n = 2), lung cancers, MRCLS, melanoma. Progressive disease (PD, n = 3, 13.6%) was seen in EGJ. lung and ovarian cancers. Thus, overall response rate (CR, PR; n= 8) was 36.4% and the disease control rate (CR, PR, SD; n = 19) was 86.4%. As at the data cut-off, 11 patients remain on study. Of the 8 responders, 5 remained in response with some remaining progression free >24 weeks [4].
Aug 19PI SURPASS trial to assess the safety and efficacy of ADP-A2M4CD8 in patients with multiple solid tumours that express the MAGE-A4 protein starts (ADP0055-001; NCT04044859). The three-cohort dose escalation trial will enrol 60 patients who have the appropriate human leukocyte antigen (HLA) and tumor antigen status and whose urothelial, head and neck, gastric (stomach), esophagogastric junction (EGJ), non-small cell lung (NSCLC), esophageal or ovarian cancer express the MAGE-A4 protein. Enrolment is underway in the US, Belgium, Canada and Spain (no UK sites). An expansion phase with higher doses will follow the dose escalation phase. Patients will be given an infusion of autologous genetically modified ADP-A2M4CD8 on Day 1. Primary outcome is safety, including incidence of treatment-related adverse events and measurement of replication-competent retrovirus in genetically engineered T-cells at 15 years, evaluated using PCR -based assay in peripheral blood; collection of these data is due to complete Sep 23 [3].