Phase III data show Hernexeos can elicit a confirmed objective response rate of 48% in patients with HER2-mutated NSCLC who had previously been treated with a directed antibody-drug conjugate.
The FDA signed off on Boehringer Ingelheim’s kinase inhibitor zongertinib for the treatment of certain patients with non-small cell lung cancer. The drug, to be marketed under the brand name Hernexeos, marks Boehringer Ingelheim’s debut in the cancer space after 140 years in business.
Hernexeos is specifically indicated for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC), whose tumors harbor HER2 tyrosine kinase domain (TKD)-activating mutations, according to the FDA’s announcement of the approval on Friday. The regulator cleared Hernexeos under its accelerated pathway. The drug’s continued approval will be contingent on a confirmatory trial.
Data from the Phase I Beamion LUNG-1 trial supported Friday’s approval. Data published in September 2024 showed Hernexeos elicited a 66.7% objective response rate (ORR), as well as an intracranial response rate of 33% in patients with brain metastases. In this subpopulation, disease control rate was 74%.
Boehringer released updated and more detailed data earlier this year, showing that in patients with TKD mutations, the confirmed ORR was 71%, with a median progression-free survival of 12.4 months. Meanwhile, confirmed ORR was 48% in patients with TKD mutations who had previously been treated with a HER2-directed antibody-drug conjugate.
Hernexeos was also safe overall, as per the early-stage readout, with only 2.9% of treated patients dropping out of the trial. There were no documented instances of drug-related interstitial lung disease.
Shashank Deshpande, head of Human Pharma at Boehringer, said in a statement on Friday that Hernexeos has the “potential to reset the benchmark for those living with HER2-mutant advanced non-small cell lung cancer,” adding that the disease is often associated with a poor prognosis. Patients with metastatic NSCLC face a 5-year survival rate of less than 10%, according to data from the National Cancer Institute. HER2 mutations, which occur in 2% to 4% of all NSCLC cases, are linked to worse prognoses and brain metastasis.
Designed to be taken orally, Hernexeos addresses an underlying disease pathway in NSCLC by selectively and irreversibly binding to HER2, in turn preventing cell growth and division dependent on this signaling cascade.
With its approval on Friday, Hernexeos will join AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu in the HER2-mutant NSCLC arena. Enhertu was approved for this indication in August 2022 and is also indicated for different types of breast cancer and HER2-positive solid tumors. Last year, Enhertu made nearly $2 billion worldwide.
