Analytical and Clinical Validation of the Oncomine Dx Target Test to Assess HER2 Mutation Status in Tumor Tissue Samples From Patients With Non-Small Cell Lung Cancer Treated With Trastuzumab Deruxtecan in the DESTINY-Lung01 and DESTINY-Lung02 Studies.

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-targeted therapy, has demonstrated durable anticancer activity in patients with advanced, metastatic HER2 (also known as ERBB2)-mutant (HER2m) non-small cell lung cancer (NSCLC) who have limited treatment options and poor prognosis. To analytically validate and assess the clinical utility of the Oncomine Dx Target (ODxT) Test as a companion diagnostic to identify patients with HER2m NSCLC. Tumor samples from patients in DESTINY-Lung01 and DESTINY-Lung02 were retrospectively analyzed alongside commercially procured samples using the ODxT test and compared to the assays used for screening in these clinical trials. Positive percent agreement (PPA) and negative percent agreement (NPA) between the ODxT Test and TruSight Tumor 170 assay when testing DESTINY-Lung01 and commercially procured samples met prespecified thresholds (PPA and NPA ≥90%) for analytical accuracy (100% and 99.1%). The ODxT Test results were highly concordant with clinical trial assays (CTAs) used in DESTINY-Lung01 (PPA and NPA, 98.0% and 100%) and DESTINY-Lung02 (PPA and NPA, 96.7% and 100%) to identify activating HER2 mutations in tumor samples. Confirmed objective response rates were similar between patients with HER2m tumors identified by the ODxT Test and by CTAs in DESTINY-Lung01 (58.3% and 54.9%) and DESTINY-Lung02 (53.6% and 53.8%). Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01. The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

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Karnoub, Pereira, and Shiga are employees of Daiichi Sankyo, Inc. Qi, Feng, and Khambata-Ford are employees of and hold stock and stock options in Daiichi Sankyo, Inc. Ha and Velasco Roth are employees of Thermo Fisher Scientific. Smit has received consulting fees paid to his institution from Daiichi Sankyo, Inc, and has participated in advisory boards for Daiichi Sankyo, Inc. Y. Goto has received research grants paid to his clinical trial group or institution from Daiichi Sankyo, Inc, speaker payments or honoraria from Thermo Fisher Scientific, and has participated in advisory boards for Daiichi Sankyo, Inc. K. Goto has received research grants paid to his institution from Daiichi Sankyo, Inc, speaker payments or honoraria from Daiichi Sankyo, Inc, and Thermo Fisher Scientific, and has participated in advisory boards for Daiichi Sankyo, Inc. De Langen has no relevant financial interest in the products or companies described in this article.