GlobalData, a data and analytics company, has reported that further development of chimeric antigen receptor (CAR)-T cell therapies in solid tumours will require collaboration with industry.
market analysis
Just as Seattle Children’s Hospital (SCH) has initiated a study of two CAR-T cell therapies in young people with relapsed or refractory (R/R) non-central nervous system epidermal growth factor receptor (EGFR)-positive solid tumours, GlobalData states that if study data are positive, collaboration with industry will be required to support further clinical development and commercialisation.
Success of CAR-T cell therapies so far has been limited to haematological malignancies, with unprecedented efficacy being demonstrated. However, CAR-T cell expansion rates in solid tumours have remained low and appear to be a limiting factor for the therapy’s efficacy.
The only therapy that has received a tumour-agnostic approval from the US Food and Drug Administration (FDA) for any solid tumour that is either microsatellite instability-high or mismatch repair deficient has been Merck’s Keytruda (pembrolizumab).
Reportedly, of the 25 ongoing clinical trials evaluating EGFR-targeted CAR-T cells in solid tumours, SCH’s is the only study in which the CAR-T product is also engineered to target CD19. Targeting CD19-positive B-cells is hypothesized to enhance T-cell expansion by promoting an immune response and therefore aims to increase the efficacy of the CAR-T cell therapy.
“The SCH’s approach of using a B-cell target to enhance immune response could overcome this major hurdle in the development of CAR-T cell therapies in solid tumours,” stated Chloé Thépaut, senior healthcare analyst at GlobalData. “Although a high cure rate can be achieved in most solid tumours, except for brain tumours, with other treatments such as surgery, long-term survival is lower for R/R patients.”
The approach being adopted by SCH may mean that the difficulties of ensuring CAR-T cell expansion may be overcome and it could allow an enhanced efficacy in solid tumours. As the Phase I/II trial is set to include patients with multiple EGFR-positive tumour types, if the researchers are able to demonstrate pan-tumour efficacy then a significant commercial opportunity for a broad label may arise.
“Many unmet needs remain for young patients with solid tumours, and academic institutions globally are turning to immuno-oncology research to improve outcomes,” concluded Thépaut. “If data from the SCH’s new study are positive, collaboration with industry will likely be required to support further clinical development and commercialisation of anti-EGFR/CD19 CAR-T cell therapy.”