Today, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zongertinib (Hernexeos), a kinase inhibitor, for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD)–activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.
The FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 TKD–activating mutations in patients with nonsquamous NSCLC who may be eligible for treatment with zongertinib.
Beamion LUNG-1
Efficacy was evaluated in patients with unresectable or metastatic nonsquamous NSCLC with HER2 TKD mutations who had received prior systemic therapy and received zongertinib in Beamion LUNG-1 (ClinicalTrials.gov identifier NCT04886804), an open-label, multicenter, multicohort trial. The major efficacy outcome measures were objective response rate and duration of response determined by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1.
Among 71 patients who received prior platinum-based chemotherapy but had not been previously treated with a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate (ADC), the objective response rate was 75% (95% confidence interval [CI] = 63%– 83%), with 58% having a duration of response lasting at least 6 months.
Among 34 patients previously treated with platinum-based chemotherapy and a HER2-targeted ADC, the objective response rate was 44% (95% CI = 29%–61%), with 27% having a duration of response lasting at least 6 months.
The prescribing information for zongertinib includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryofetal toxicity.
The recommended zongertinib dose is based on body weight. For patients weighing < 90 kg, the dose is 120 mg orally once daily; for patients weighing ≥ 90 kg, the dose is 180 mg orally once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review. Zongertinib received Breakthrough Therapy and Fast Track designations.
