Zongertinib Tablets Enter Priority Review for Treating HER2-Mutant NSCLC

According to the CDE website on December 25, Boehringer Ingelheim’s (BI) oral HER2 inhibitor Zongertinib tablets (BI 1810631) have been proposed for inclusion in the priority review process. The drug is intended for treating unresectable or metastatic HER2-mutant non-small cell lung cancer (NSCLC) in adult patients who have undergone prior systemic therapy.

Zongertinib is a selective HER2 inhibitor that covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including those with exon 20 mutations. This enhanced selectivity may lead to better tolerability and efficacy. The drug had previously been granted Breakthrough Therapy Designation by the CDE.

In April this year, Boehringer Ingelheim signed a strategic collaboration agreement with China Biopharma. The two companies will leverage their resources to co-develop and commercialize BI's oncology drug pipelines in mainland China, including Zongertinib.

Research indicates that 2%-4% of NSCLC patients in China exhibit HER2 gene mutations. Historically, HER2-mutant NSCLC patients have had poor prognoses, with median overall survival (OS) following a stage IV diagnosis at only 1.6–1.9 years and progression-free survival (PFS) shorter than that of EGFR-mutant and ALK/ROS1-rearranged NSCLC patients.

Beamion LUNG-1, a Phase Ia/Ib first-in-human open-label trial (NCT04886804), included a Phase Ia dose-escalation study evaluating Zongertinib’s efficacy in patients with advanced/metastatic solid tumors harboring any HER2 alteration. The trial identified 120 mg and 240 mg QD as the recommended expansion doses.

As of May 23, 2024, a total of 132 patients in the Ib cohort received Zongertinib at daily doses of 120 mg or 240 mg (n=75/57). Independent Central Review Committee (BICR) evaluations confirmed an objective response rate (ORR) of 66.7%, and tumor reduction of varying magnitudes was observed in 94% of patients across all dose groups.