The FDA has granted simultaneous approval for HERNEXEOS (zongertinib tablets), developed and commercialized by Boehringer Ingelheim, for the treatment of adult patients with non-small cell lung cancer (NSCLC). The approval covers tumors with HER2 (ERBB2) activating mutations. It also signed off on Thermo Fisher Scientific’s Oncomine Dx Target Test as a companion diagnostic (CDx) to determine which patients may be eligible for this targeted therapy.
HERNEXEOS is the only orally administered therapy for adult patients with unresectable and metastatic non-squamous NSCLC whose tumors have HER2 tyrosine kinase domain-activating mutations. This form of lung cancer is rare, with approximately 2-4% of NSCLC patients having a HER2 mutation. The mutation has been linked to poor prognosis and limited treatment options. The estimated five-year survival rate is less than 10%, according to a 2025 study.
“Boehringer Ingelheim is committed to developing therapies for hard-to-treat cancers and where there is significant unmet need,” Vicky Brown, Senior Vice President and Head of Oncology, Immunology and Eye Health at Boehringer Ingelheim, said in an email to Drug Discovery and Development.
HERNEXEOS was granted Breakthrough Therapy Designation, which fast-tracked the drug’s approval as part of the Priority Review and Accelerated Approval programs.
Shrinking tumors through high selectivity
“One of the biggest challenges was to get high selectivity to HER2, and the large number of similarities between HER2 and EGFR made it particularly difficult,” said Brown.
To solve this challenge, the team was able to identify a single amino acid that is different in the compound binding pocket of HER2 and EGFR, which allowed them to design compounds that were selective for HER2.
HERNEXEOS selectively inhibits HER2 while sparing wild-type EGFR. The drug binds to the tyrosine kinase domain of both wild-type and mutated HER2 receptors, blocking the signals that cause cancer cells to grow.
In the Beamion LUNG-1 trial, 75% of patients saw measurable tumor shrinkage, with 6% seeing their tumor disappear completely.
Boehringer Ingelheim is also investigating HERNEXEOS across a range of cancer types and advanced solid tumors with HER2 mutations. The drug is currently in clinical trials for unresectable or metastatic HER2 (ERBB2)-mutant NSCLC.
Last month, Boehringer Ingelheim reported new data from the clinical trial that demonstrated a confirmed intracranial objective response rate of 43% in patients with active brain metastases. Approximately 50% of patients with HER2-mutant NSCLC develop brain metastases, which have a median overall survival of less than six months.
Determining potential patients
The Oncomine Dx Target Test is a companion diagnostics test (CDx) that identifies key genetic mutations in patients. It is currently approved by the FDA for 11 CDx across four indications. CDx provides genetic information to help healthcare professionals determine whether a precision medicine or therapy will benefit a patient.
“Overall, the approval means that patients will have increased access to both the quick and reliable diagnostic test and targeted therapy, greatly improving treatment options for those with NSCLC and who previously had limited choices,” said Jane Li, Senior Director, Pharma CDx and CRO Partnership, Thermo Fisher Scientific, in an email to Drug Discovery and Development.
These approvals are part of a larger trend towards precision medicine. The integration of AI into data analysis and clinical trial design is enabling rapid advances in the field. AI can help researchers understand the large datasets involved in healthcare data and multiomics, which are vital in precision medicine.
According to a Precedence Research report, the global precision medicine market size is predicted to reach around USD 470.53 billion by 2034. The market size is improving at a compound annual growth rate (CAGR) of 16.50% from 2025 to 2034.
Filed Under: Oncology
