Pan-tumor validation of FoundationOne®CDx as a companion diagnostic for RET fusions as a predictor of response to selpercatinib.

BACKGROUND

RET fusions represent a subgroup of alterations in cancer biology that exhibit sensitivity to selective RET kinase inhibitors. We analytically validated a next-generation sequencing-based companion diagnostic (CDx) to detect RET fusions in solid tumors via a comprehensive genomic profiling assay, FoundationOne®CDx (F1CDx®).

METHODS

The F1CDx assay produces chimeric read pairs to determine fusion status. Additionally, a study of F1CDx was conducted as a retrospective clinical bridging study based on LIBRETTO-001 clinical trial samples and data.

RESULTS

Across solid tumor types, F1CDx demonstrated a high concordance for RET fusion detection with both an externally validated assay and LIBRETTO-001 clinical trial assays with positive percent agreements of 100.0% (146/146) and 90.80% (79/87), negative percent agreements of 97.3% (254/261) and 100.0% (138/138), and overall percent agreements of 98.2% (400/407) and 96.44% (213/225), respectively. Based on LIBRETTO-001 clinical data, the objective response rate to selpercatinib for patients with tumors harboring RET fusions as determined by F1CDx was estimated to be 69.62%. Demonstrated analytical and clinical performance of F1CDx led to the pan-tumor approvals from the U.S. Food and Drug Administration (FDA) in 2023 and the Japan Ministry of Health, Labour and Welfare (MHLW) in 2024 of F1CDx to identify RET fusions in solid tumor patients for treatment with selpercatinib.

CONCLUSIONS

F1CDx is an accurate, reliable, FDA- and MHLW-approved method for the pan-tumor identification of RET fusions for treatment with selpercatinib.