The U.S. Food and Drug Administration (FDA) has approved Hernexeos (zongertinib tablets, 60 mg) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test.
Accelerated approval is based on data from a cohort of treatment-naïve patients (N=72) in the phase 1b Beamion LUNG-1 trial, which demonstrated an objective response rate of 76%, including 11% of patients with a complete response and 65% of patients with a partial response. Zongertinib demonstrated a duration of response of greater than or equal to six months in 64% of patients.
“Zongertinib is setting a new standard as the first targeted therapy for treatment-naïve patients with HER2-mutated advanced non-small cell lung cancer with demonstrated efficacy, a manageable safety profile and once-daily oral administration,” said John Heymach, MD, PhD, coordinating investigator for the Beamion LUNG-1 trial and chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “Now these patients finally have a targeted treatment option that they can receive immediately following identification of a HER2 mutation.”
According to a press release from drug developer Boehringer Ingelheim, HER2 mutations occur in approximately 2–4% of NSCLC cases and are associated with a poor prognosis and higher incidence of brain metastases. Alterations in the HER2 gene, including mutations, amplification and overexpression, trigger uncontrolled cell proliferation — inhibiting cell death and promoting tumor growth and spread.
“We first learned about the HER2 genetic mutation as a lung cancer driver in a small subset of patients more than 20 years ago. Half of these people do not respond to the current standard of care, which is why it is vital to provide them with a treatment option that has been designed specifically for their disease,” said Danielle Hicks, chief patient officer of GO2 for Lung Cancer. “Understanding your biomarkers is so important because it can unlock more personalized and effective treatment options.”
Hernexeos is an irreversible tyrosine kinase inhibitor that inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities. With the FDA approval, it becomes the first orally administered, targeted therapy for adults with HER2-mutated NSCLC. Comprehensive biomarker testing using next generation sequencing determines a patient’s eligibility for treatment with Hernexeos by identifying the HER2 mutations associated with advanced NSCLC.
Currently, the therapy is under evaluation in ongoing trials across a range of earlier stages and advanced solid tumors with HER2 alterations. Beamion LUNG-2 is an ongoing phase 3 controlled study investigating zongertinib as a first-line treatment for patients with advanced NSCLC with HER2 tyrosine kinase domain mutations. Beamion LUNG-3 is a phase 3 clinical trial investigating zongertinib as an adjuvant monotherapy in patients with early-stage, resectable NSCLC (stage 2–3B) with HER2 mutations.
