The FDA has approved the Ion Torrent Oncomine Dx Target Test for use as a companion diagnostic to identify patients with non–small cell lung cancer (NSCLC) and select HER2 (ERBB2) TKD activating mutations who are eligible for treatment with sevabertinib (Hyrnuo).1
The HER2-directed therapy received accelerated approval on November 19, 2025, amid a flurry of other key regulatory decisions, for use in this population based on data from groups D and E of the phase 1/2 SOHO-01 trial (NCT05099172).2,3 In those within group D with nonsquamous NSCLC and HER2 TKD mutations who had previous systemic therapy but were naive to HER2-targeted therapy (n = 70), sevabertinib elicited an objective response rate (ORR) of 71% (95% CI, 59%-82%), which included a complete response (CR) rate of 2.9% and a partial response (PR) rate of 69%. The median duration of response (DOR) was 9.2 months (95% CI, 6.3-15.0); 54% of patients experienced a response that lasted for at least 6 months and 18% experienced a response that lasted for at least 12 months.
Moreover, in group E, which comprised those who received prior treatment, including HER2-targeted antibody-drug conjugates (n = 52), the agent elicited an ORR of 38% (95% CI, 25%-53%); the CR and PR rates were 6% and 33%, respectively. The median DOR was 7.0 months (95% CI, 5.6-not evaluable); the observed proportion of responding patients with a DOR of at least 6 or at least 12 months was 60% and 10%, respectively.
“We are committed to advancing innovation for patients with difficult-to-treat cancers, and this approval marks another step forward in ensuring all patients with cancer have access to optimal treatment options,” Emmanuelle Di Tomaso, vice president, global head of Translational Sciences Oncology at Bayer, stated in a news release.1 “Collaborating with Thermo Fisher to leverage the Oncomine Dx Target Test allows us to ensure clinical teams can identify patients who are most likely to benefit from sevabertinib, supporting timely and informed treatment decisions in real-world clinical settings.”
What is the Oncomine Dx Target test?
The Ion Torrent Oncomine Dx Test became the first distributable next-generation sequencing (NGS)–based in vitro diagnostic test, when it was approved by the FDA in 2017.4 According to ThermoFisher Scientific, the test allows for shorter turnaround times with regard to results to inform treatment decisions, helps to automate workflows, and requires low sample input. The test is able to identify patients for several approved therapies in the following disease areas:5
- NSCLC: Dabrafenib (Tafinlar) plus trametinib (Mekinist), gefitinib (Iressa), amivantamab-vmjw (Rybrevant), fam-trastuzumab deruxtecan-nxki (Enhertu), pralsetinib (Gavreto), selpercatinib (Retevmo), crizotinib (Xalkori)
- Cholangiocarcinoma: Ivosidenib (Tibsovo)
- Anaplastic thyroid cancer: Dabrafenib plus trametinib
- Astrocytoma and Oligodendroglioma: Vorasidenib (Voranigo)
- Medullary thyroid cancer: Selpercatinib
- Thyroid cancer: Selpercatinib
What are the top takeaways from the SOHO-01 trial that led to the approval of sevabertinib?
Groups D and E of the open-label, single-arm, multicenter, multicohort study included patients with previously treated locally advanced or metastatic NSCLC with HER2 activating mutations and an ECOG performance status of 0 or 1.3 Those with treated, stable, and asymptomatic brain metastases could enroll, but those with symptomatic central nervous system metastases, significant cardiac disease, or a history of interstitial lung disease that was dependent on steroids, could not.
Participants were administered sevabertinib at a twice-daily dose of 20 mg, with treatment continuing until progressive disease or intolerable toxicity. The primary end points of the study were confirmed ORR and DOR, both per blinded independent central review assessment and using RECIST 1.1 criteria.
Of the 122 total patients in the combined cohorts, 67.2% of tumor tissue samples were retrospectively tested using the Oncomine Target Test; 92.7% of these samples tested positive for HER2 TKD activating mutations and 7.3% were determined to not be evaluable. None of the samples had negative status.
Additional data presented at the 2025 ESMO Congress showed that in those within group D with nonsquamous NSCLC and HER2 TKD mutations, the median progression-free survival was 9.6 months (95% CI, 6.9-14.7).6
In terms of safety, treatment-related adverse effects (TRAEs) were experienced by 96% of those in group D overall and all of those in group E overall. The most common grade 1/2 and grade 3 TRAEs, respectively, reported in group D overall (n = 81) were diarrhea (63%; 23%), rash (49%; 1%), paronychia (27%; 0%), stomatitis (17%; 1%), nausea (19%; 3%), hypokalemia (12%; 4%), vomiting (14%; 4%), anemia (15%; 1%), decreased weight (17%; 0%), increased alanine aminotransferase level (15%; 1%), dry skin (17%; 0%), increased aspartate aminotransferase (16%; 1%), pruritus (17%; 3%), decreased appetite (11%; 4%), increased amylase (15%; 0%), and increased lipase (12%; 0%).
No cases of interstitial lung disease (ILD) or pneumonitis were observed. However, the prescribing information for sevabertinib does include warnings and precautions regarding ILD/pneumonitis, diarrhea, hepatotoxicity, ocular toxicity, pancreatic enzyme elevation, and embryo-fetal toxicity.2
In an exclusive interview with OncLive® at the congress, Xiuning Le, MD, PhD, an associate professor in the Department of Thoracic/Head and Neck Medical Oncology of the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center, further discussed SOHO-01 data and its significance:7 “In the clinical part, we were able to show very good response rate [with sevabertinib] regardless of prior lines of therapy. Overall, we think that this agent is very promising as a new option for patients with HER2-mutant lung cancer,” she said.
