FDA Approves Companion Diagnostic for Trastuzumab Deruxtecan in HER2-Mutated Non-Small Cell Lung Cancer


The Oncomine Dx Target Test is a next-generation sequencing–based companion diagnostic developed to analyze 23 genes associated with non–small cell lung cancer in patients who harbor an activating HER2 mutation.

The FDA granted approval to the Oncomine Dx Target Test as a companion diagnostic to identify patients with non–small cell lung cancer (NSCLC) who harbor an activating human epidermal growth factor receptor 2 (HER2) mutation who may gain clinical benefit from fam-trastuzumab deruxtecan-nxki (Enhertu).1

Earlier this month, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo, Inc) for adult patients with unresectable or metastatic NSCLC. To be eligible for treatment, patients with NSCLC must have tumors that activate HER2 (ERBB2) mutations and have had prior systemic therapy. The recommended dose is 5.4 mg/kg every 3 weeks.

The Oncomine Dx Target Test is a next-generation sequencing (NGS)–based companion diagnostic developed to analyze 23 genes associated with NSCLC. The FDA initially approved the companion diagnostic in 2017, and it has subsequently been approved for 7 targeted therapies for NSCLC and 1 for cholangiocarcinoma.

“With care decisions increasingly made based on a tumor’s molecular profile, the FDA’s latest approval of [trastuzumab deruxtecan] in HER2-mutant metastatic NSCLC and the additional approval of the Oncomine Dx Target Test as a companion diagnostic marks a significant step forward for precision oncology,” said Garret Hampton, president of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher Scientific, in a statement. “To ensure patients and clinicians can readily access testing to inform care decisions, we are committed to making NGS accessible and easy to use so patients everywhere will be able to benefit from precision therapies, when indicated.”

The approval was based on findings from DESTINY-Lung02 (NCT04644237), a multicenter, multicohort, randomized, blinded, dose-optimization phase 2 trial. In the trial, patients with unresectable or metastatic HER2-mutant nonsquamous NSCLC who had disease progression after prior systemic therapy (n = 52) who were administered trastuzumab deruxtecan at a dose of 5.4 mg/kg every 3 weeks experienced a confirmed overall response rate (ORR) of 58% (95% CI, 43%-71%) with a median duration of response (DOR) of 8.7 months (95% CI, 7.1–not estimable).

The trial included patients at least 18 years of age with unresectable or metastatic HER2-mutant NSCLC. Eligible patients were previously administered platinum-based chemotherapy in the metastatic/locally advanced setting and were not amenable to curative surgery or radiation. Patients were also required to have an ECOG performance status of 0 or 1, an adequate treatment washout period before randomization, and a life expectancy of at least 3 months.2

Patients were excluded from the trial if they had a known EGFRBRAF, or MET exon 14 driver mutation, or a known ALKROS1RET, or NTRK fusion; a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids; current or suspected ILD/pneumonitis that could not be ruled out by imaging at screening; or a medical history of myocardial infarction within 6 months prior to randomization or symptomatic congestive heart failure.

Patients were randomized to 5.4 mg/kg or 6.4 mg/kg trastuzumab deruxtecan every 3 weeks. The primary end point of the trial was ORR by blinded independent central review, with secondary end points of investigator-assessed ORR, DOR, disease control rate, progression-free survival, overall survival, and safety.

The most common adverse effects (AEs) experienced by 20% or more of patients included decreased white blood cell count, hemoglobin, neutrophil count, lymphocyte count, platelet count, and albumin. Other commonly experienced AEs were increased aspartate aminotransferase, increased alanine aminotransferase, nausea, fatigue, constipation, decreased appetite, vomiting, increased alkaline phosphatase, and alopecia.


  1. FDA approves first NGS-based companion diagnostic to aid in selecting non-small cell lung cancer patients with HER2 (ERBB2) activating mutations (SNVs & exon 20 insertions) for treatment with Enhertu. News release. Thermo Fisher Scientific. August 12, 2022. Accessed August 16, 2022. https://bwnews.pr/3STT1s9
  2. Trastuzumab deruxtecan in participants with HER2-mutated metastatic non-small cell lung cancer (NSCLC) (DESTINY-LUNG02). ClinicalTrials.gov. Updated April 29, 2022. Accessed August 16, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04644237
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