The primary objective of the trial is to assess the safety and tolerability of cNeT as monotherapy and in combination with pembrolizumab, and will also evaluate the clinical efficacy as a secondary measure. Additional data evaluating cNeT persistence, phenotype, and functionality will be reviewed while also exploring potential biomarkers of clinical activity and factors affecting response. This will include analysis of patient samples using a bespoke plasma ctDNA assay.
''With 75% of patients with NSCLC presenting with inoperable or metastatic disease and a 5-year survival for stage IV disease as low as 5%, additional treatments are needed for this large patient population including autologous cell therapies like Achilles' cNeT,'' commented Dr. Jamal-Hanjani. ''The rationale of the CHIRON trial is very evident as we know that NSCLC patients with tumours that have a high burden of clonal neoantigens have improved disease free survival and increased sensitivity to checkpoint inhibition.''
''Just as with our THETIS melanoma trial, CHIRON allows us to look at the safety and tolerability of our precision cNeT as monotherapy and in combination with a checkpoint inhibitor,'' said Dr. Peggs, CMO of Achilles. ''While the primary purpose of the trials is safety, the addition of these checkpoint combination cohorts will allow further examination of T cell kinetics and the contribution of cell dose and checkpoint therapy to treatment outcomes. Further, we will continue to look at the predictive value of ctDNA as a potential marker for clinical events as we look towards the future of our product with potential companion diagnostics in addition to our planned potency assays.''
All patients enrolled in CHIRON will have been treated with at least one prior systemic therapy, inclusive of a checkpoint inhibitor unless contraindicated, have an ECOG Status 0-1, have locally advanced or metastatic disease, and have accessible sites for collection of adequate tissue. Patients requiring regular immunosuppression (including steroids at a dose equivalent to prednisolone 10 mg/day or greater) or that have previously received any investigational cell or gene therapies are not eligible.
