FDA Approves Oncomine Dx Target Test as Zongertinib Companion Diagnostic in Nonsquamous NSCLC With HER2 TKD Mutations

The FDA has approved the Oncomine™ Dx Target Test as a companion diagnostic for the identification of patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD)–activating mutations and may benefit from treatment with zongertinib (Hernexeos).¹

On August 8, 2025, the FDA granted accelerated approval to zongertinib for adult patients with unresectable or metastatic nonsquamous NSCLC whose tumors express HER2 TKD activating mutations and who have received prior systemic therapy, making zongertinib the first and only orally administered targeted therapy for this patient population.

This regulatory decision was supported by findings from the phase 1 Beamion LUNG-1 trial (NCT04886804), in which evaluable patients who received prior platinum-based chemotherapy and had not been previously treated with a HER2-targeted TKI or antibody-drug conjugate (n = 71) achieved an overall response rate (ORR) of 75% (95% CI, 63%-83%).² The 6-month duration of response (DOR) rate was 58%. Among those who previously received platinum-based chemotherapy and a HER2-targeted ADC (n = 34), the ORR was 44% (95% CI, 29%-61%) and the 6-month DOR rate was 27%.

“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,” Vicky Brown, senior vice president and head of Immunology, Oncology, and Eye Health at Boehringer Ingelheim, stated in a news release. “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 (ERBB2) [TKD] –activating mutations in NSCLC.”

In addition to its newly acquired indication as a companion diagnostic for zongertinib, the Oncomine Dx Target Test has been granted regulatory approval in 20 countries for 11 biomarkers and over 20 targeted therapies. For the United States–based population, this includes targeted therapies in NSCLC, cholangiocarcinoma, astrocytoma, and oligodendroglioma, anaplastic thyroid cancer, medullary thyroid cancer, and thyroid cancer.¹

“The FDA’s approval of [zongertinib] for previously treated patients living with HER2 (ERBB2)-mutant advanced NSCLC signifies continued success in our efforts to develop timely and accessible companion diagnostics,” Kathy Davy, president of clinical next-generation sequencing [NGS] at Thermo Fisher Scientific, added. “We’re 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.”

Beamion LUNG-1 Trial Overview

Beamion LUNG-1 is an open-label, dose-escalation and dose-expansion study that evaluated zongertinib monotherapy in adult patients with advanced NSCLC harboring HER2 TKD alterations.³ Eligible patients had histologically or cytologically confirmed unresectable or metastatic non-hematologic malignancies; displayed HER2 mutations; had at least 1 measurable lesion per RECIST 1.1 criteria; and had an ECOG performance status of 0 or 1.

During the dose-escalation phase, patients received increasing doses of zongertinib to determine the maximum tolerated dose (MTD). The expansion phase evaluated the optimal dose for efficacy and safety in HER2-mutant nonsquamous NSCLC after prior systemic therapy.

The study’s primary end points were the incidence of dose-limiting toxicities in phase 1a and ORR in phase 1b. DOR, progression-free survival, disease control rate, overall survival (OS), safety, and pharmacokinetics, served as key secondary end points.

Notably, the phase 3 Beamion LUNG-2 trial (NCT06151574) comparing zongertinib with standard-of-care therapy in the first line for patients with HER2 TKD–mutant unresectable or metastatic nonsquamous NSCLC is currently ongoing.⁴

References

1. Thermo Fisher receives FDA approval for NGS-based companion diagnostic for new non-small cell lung cancer treatment.News release. Thermo Fisher. August 11, 2025. Accessed August 11, 2025. https://newsroom.thermofisher.com/newsroom/press-releases/press-release-details/2025/Thermo-Fisher-Receives-FDA-Approval-for-NGS-Based-Companion-Diagnostic-for-New-Non-Small-Cell-Lung-Cancer-Treatment/default.aspx
2. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed August 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations
3. Beamion LUNG-1: a study to test different doses of zongertinib in people with different types of advanced cancer (solid tumours with changes in the HER2 gene). ClinicalTrials.gov. Updated July 28, 2025. Accessed August 11, 2025. https://clinicaltrials.gov/study/NCT04886804
4. Beamion LUNG-2: a study to testwWhether zongertinib (BI 1810631) helps people With advanced non-small cell lung cancer with HER2 mutations compared with standard treatment. ClinicalTrials.gov. Updated August 6, 2025. Accessed August 11, 2025. https://clinicaltrials.gov/study/NCT06151574?term=NCT06151574&rank=1