FDA Grants Priority Review to Sevabertinib in HER2-Mutant NSCLC

Efficacy results revealed that among patients with HER2-mutant NSCLC treated with sevabertinib, the objective response rate was 72.1%, and the disease control rate was 83.7%.

The FDA has accepted and granted priority review to a new drug application for sevabertinib (BAY 2927088) as a treatment for patients with previously treated advanced HER2-mutant non–small cell lung cancer (NSCLC), according to a press release from the drug’s developer, Bayer.1

Support for the decision is based on data from the phase 1/2 SOHO-01 trial (NCT05099172) evaluating the agent as monotherapy in patients with advanced HER2-mutant NSCLC. Results were presented at the 2024 IASLC World Conference on Lung Cancer (WCLC) and then at the 2024 Journal of the Advanced Practitioner in Oncology (JADPRO) Annual Meeting.2

Efficacy results revealed that among patients with HER2-mutant NSCLC treated with sevabertinib (n = 43), the objective response rate (ORR) was 72.1% (95% CI, 56.3%-84.7%), and the disease control rate (DCR) was 83.7% (95% CI, 69.3%-93.2%). Additionally, 2.3% of patients achieved a complete response, 69.8% attained a partial response, and 16.3% experienced stable disease.

After a median follow-up of 10.9 months (range, 0.9-20.2), 36.4% had ongoing treatment as of data cut-off, and 31.8% of patients had a treatment duration lasting more than 12 months. The median duration of treatment was 7.1 months (range, 0.2-20.2). Furthermore, the median duration of response (DOR) for this patient population was 8.7 months (95% CI, 4.5-not estimable [NE]), and the median progression-free survival (PFS) was 7.5 months (95% CI, 4.4-12.2).

A subgroup analysis for ORR revealed that patients with HER2 YVMA insertion (n = 30) achieved an ORR of 90.0% (95% CI, 73.5%-97.9%). The median PFS in this patient subgroup was 9.9 months (95% CI, 6.9-NE), and the median DOR was 9.7 months (95% CI, 5.5-NE). Additionally, those with brain metastases at baseline attained an ORR of 62.5% (95% CI, 24.5%-91.5%).

“Patients with HER2-mutant NSCLC are predominantly women, may be of younger age and non-smokers. The FDA’s decision to grant priority review designation to our application for sevabertinib is a significant milestone that supports our ongoing efforts to develop healthcare solutions that help people living with lung cancer,” Christine Roth, executive vice president of Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team at Bayer, stated in the press release.1 “If approved, sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2-activating mutation.”

Patients with advanced NSCLC with HER2 or EGFR mutations in the phase 1/2 trial were treated with increasing doses of oral sevabertinib to identify the recommended dose for expansion in the dose-escalation phase of the trial. Patients in the dose-expansion phase of the trial were treated with 20 mg of sevabertinib twice daily, and only results from cohort D, which included patients with HER2 mutations, were presented at the JADPRO Annual Meeting.

Among those with HER2-mutant NSCLC (n = 44), 63.6% were female, 68.2% were Asian, and 56.8% of patients had an ECOG performance status of 1. A total of 70.5% of this patient group had never smoked, 95.5% had adenocarcinoma, and the median time since recent relapse to initial study treatment was 1.5 months (95% CI, 0-14.4). Furthermore, 70.5% of patients had YVMA insertions, 81.8% had no brain metastases at baseline, and 31.8% of patients had 3 or more prior lines of therapy.

The primary end points of the trial were safety and tolerability, as well as pharmacokinetics. Secondary end points included investigator-assessed ORR, PFS, DOR, and DCR.

Among patients with HER2-mutant NSCLC, 95.5% had any-grade treatment-related adverse effects (TRAEs), and 43.2% experienced grade 3 or higher TRAEs. The most common any-grade TRAEs included diarrhea (86.4%), rash (43.2%), paronychia (25.0%), and nausea (25.0%). The most common grade 3 or higher TRAEs included diarrhea (25.0%), vomiting (4.5%), and decreased appetite (4.5%).

A total of 6.8% of patients had a TRAE-related discontinuation of treatment, which included single instances of epithelial microcysts, reduced visual acuity, abnormal hepatic function, and dyspnea. Furthermore, 31.8% experienced dose reductions related to TRAEs, and 11.4% of patients experienced serious TRAEs. In total, no grade 4 TRAEs and 1 grade 5 TRAE was observed, with no reports of interstitial lung disease or pneumonitis reported.

The FDA granted sevabertinib breakthrough therapy designation for patients with unresectable or metastatic HER2-mutant NSCLC in 2024.

References

1. U.S. FDA accepts new drug application under priority review for sevabertinib (BAY 2927088) in HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed May 29, 2025. https://tinyurl.com/2t5vb5ky
2. Le X, Girard N, Jänne PA, et al. Safety and efficacy of BAY 2927088 in patients with HER2-mutant NSCLC: expansion cohort from the phase I/II SOHO-01 study. Presented at the 2024 Journal of the Advanced Practitioner in Oncology (JADPRO) Annual Meeting; Grapevine, TX; November 14-17, 2024.