Seattle Children’s Hospital (SCH) has recently initiated STRIvE-01 study of two chimeric antigen receptor (CAR)-T cell therapies in young people ages 1–26, with relapsed or refractory (R/R) non-central nervous system epidermal growth factor receptor (EGFR)-positive solid tumors. The Phase 1 trial will investigate one CAR-T cell product that targets both EGFR and B-cell specific target (CD19) and another that only targets EGFR.  If data from the SCH’s new study are positive, collaboration with industry will likely be required to support further clinical development and commercialization of anti-EGFR/CD19 CAR-T cell therapy, says leading data and analytics company GlobalData.

So far, the success of CAR-T cell therapy has been limited to hematological malignancies, with unprecedented efficacy being demonstrated. However, CAR-T cell expansion rates in solid tumors have remained low and appear to be a limiting factor for the therapy’s efficacy.

To date, Merck’s Keytruda (pembrolizumab) is the only therapy to have received a tumor-agnostic approval from the FDA for any solid tumor that is either microsatellite instability-high or mismatch repair deficient, but the industry is increasingly moving towards tissue-agnostic development.

Reportedly, of the 25 ongoing clinical trials evaluating EGFR-targeted CAR-T cells in solid tumors, this 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.

Chloé Thépaut, Senior Healthcare Analyst at GlobalData, says: “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 tumors. Although a high cure rate can be achieved in most solid tumors, except for brain tumors, with other treatments such as surgery, long-term survival is lower for R/R patients.”

The SCH has adopted a scientifically rational approach that could overcome the difficulties of ensuring CAR-T cell expansion and enhance efficacy in solid tumors, thereby addressing a substantial untapped opportunity. The SCH’s Phase I/II trial will include patients with multiple EGFR-positive tumor types, which could lead to a significant commercial opportunity for a broad label, if pan-tumor efficacy is demonstrated.

Thépaut concludes: “Many unmet needs remain for young patients with solid tumors, and academic institutions globally are turning to immuno-oncology research to improve outcomes. If data from the SCH’s new study are positive, collaboration with industry will likely be required to support further clinical development and commercialization of anti-EGFR/CD19 CAR-T cell therapy.”