FDA Approves NGS-Based Companion Diagnostic for Zongertinib in NSCLC

According to developers, the CDx enables the assessment of HER2 TKD activating mutations in patients with NSCLC.

The FDA has approved the Oncomine Dx Target Test as a next-generation sequencing (NGS)–based companion diagnostic (CDx) for the identification of patients who may experience benefit with zongertinib (Hernexeos), according to a news release from the assay’s developer, Thermo Fisher Scientific.1

Previously, the drug that the companion diagnostic identifies patients for, zongertinib, received FDA accelerated approval for HER2-mutant unresectable or metastatic nonsquamous NSCLC on August 8, 2025.2 Supporting data for the decision came from the phase 1b Beamion LUNG-1 trial (NCT04886804), which assessed the agent in 71 patients who were naive to anti-HER2 tyrosine kinase inhibitors (TKIs) or antibody drug conjugates (ADCs), but who did receive prior platinum-containing chemotherapy.

The approval of the agent was based on objective response rate (ORR) and duration of response (DOR) data. The ORR in the aforementioned population was 75% (95% CI, 63%-83%), and 58% of patients experienced a DOR of 6 months or greater. Furthermore, among those who also previously received a HER2-directed ADC (n = 34), the ORR was 44% (95% CI, 29%-61%), with 27% achieving a response for at least 6 months.

Prescribing information for zongertinib highlights warning and precautions for hepatotoxicity, interstitial lung disease, left ventricular dysfunction, and embryo-fetal toxicity.

The primary efficacy end points of the phase 1b Beamion LUNG-1 trial included ORR and DOR based on blinded independent central review per RECIST v1.1 criteria. Zongertinib is currently approved at a recommended dose that is dependent on body weight, with patients weighing less than 90 kg recommended to receive 120 mg orally daily and those weighing 90 kg or more to receive 180 mg. The FDA recommends administering the agent until disease progression or unacceptable toxicities with or without food.

The continued approval of the agent in patients with NSCLC with HER2 tyrosine kinase domain (TKD) activating mutations may be contingent upon verification and description of clinical benefit in a confirmatory trial. The agent previously was granted priority reviewas a treatment for this NSCLC population in February 2025.3

"This rare form of [NSCLC] is linked to a poor prognosis and limited treatment options, making [zongertinib] an important advancement in addressing the unmet needs of patients," Victoria Brown, senior vice president and head of Immunology, Oncology, and Eye Health at Boehringer Ingelheim, said in the news release.1 “Through our collaboration with Thermo Fisher and leveraging the company’s proven track record with companion diagnostics, we’re pleased that patients have another tool that can be used to identify those with HER2 [TKD] activating mutations in [NSCLC].”

According to developers, the CDx enables the assessment of HER2 TKD activating mutations in patients with NSCLC. The Oncomine Dx Target Test, which was initially approved as an NGS-based CDx in 2017, has since received approvals in 20 countries for 11 biomarkers and over 20 targeted therapies. In the US, it is also approved for cholangiocarcinoma, astrocytoma, oligodendroglioma, anaplastic thyroid cancer, medullary thyroid cancer, and thyroid cancer.

"The FDA's approval of [zongertinib] for previously treated patients living with HER2-mutant advanced [NSCLC] signifies continued success in our efforts to develop timely and accessible companion diagnostics," Kathy Davy, president of clinical next-generation sequencing at Thermo Fisher Scientific, concluded in the news release.1 “We are continuing to expand our solutions for our pharma partners, as this approval quickly follows the recent FDA approval of our latest rapid NGS solution that can deliver results in as little as 24 hours.”

References

1. Thermo Fisher receives FDA approval for NGS-based companion diagnostic for new non-small cell lung cancer treatment. News release. Thermo Fisher Scientific. August 11, 2025. Accessed August 12, 2025. https://tinyurl.com/3h73v3en
2. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. FDA. August 8, 2025. Accessed August 12, 2025. https://tinyurl.com/bdh2d4uc
3. Boehringer's zongertinib receives priority review from U.S. FDA for the treatment of HER2 (ERBB2)-mutant advanced non-small cell lung cancer. News release. Boehringer Ingelheim. February 19, 2025. Accessed August 12, 2025. https://tinyurl.com/4475t495