FDA Grants Accelerated Approval to Zongertinib for NSCLC With HER2 TKD-Activating Mutations

The FDA has granted accelerated approval to zongertinib (Hernexeos, Boehringer Ingelheim Pharmaceuticals, Inc) for unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain (TKD)–activating mutations.

The approval is for patients who have HER2 TKD-activating mutations as detected by an FDA-approved test and who have received prior systemic therapy.

In conjunction, 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.

The efficacy of zongertinib was evaluated in Beamion LUNG-1, an open-label, multicenter, multi-cohort trial. The trial included patients with unresectable or metastatic, nonsquamous NSCLC with HER2 TKD mutations who had received prior systemic therapy, FDA officials explained in a press release. The major efficacy outcome measures of Beamion LUNG-1 were objective response rate (ORR) and duration of response (DOR) determined by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

The ORR was 75% (95% CI, 63%-83%) in the 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), with 58% having a DOR of at least 6 months.

The ORR was 44% (95% CI, 29%-61%) in the 34 patients who previously received treatment with platinum-based chemotherapy and a HER2-targeted ADC, with 27% having a DOR of at least 6 months.

The prescribing information for zongertinib includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The recommended zongertinib dose is based on body weight, FDA officials explained. For patients weighing less than 90 kg, the dose is 120 mg orally once daily. For patients weighing  90 kg or more, the dose is 180 mg orally once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity occurs.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission before 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 previously received breakthrough therapy designation and fast track designation.