The U.S. Food and Drug Administration (FDA) has accepted and granted priority review to a new drug application (NDA) for the investigational compound sevabertinib (BAY 2927088), in adult patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose tumors have activating HER2 mutations, according to a news release from Bayer.
“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,” said Christine Roth. “If approved, sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2-activating mutation.”
Roth is the executive vice president of Global Product Strategy and Commercialization, as well as a member of the Pharmaceutical’s Leadership Team at Bayer.
The NDA for sevabertinib is supported by findings from the ongoing phase 1/2 SOHO-01 trial, which includes patients with advanced NSCLC and HER2-activating mutations. Participants had experienced disease progression after at least one prior systemic therapy for advanced disease and had not received HER2-targeted treatment.
Glossary
Tyrosine kinase inhibitor (TKI): type of drug that blocks enzymes involved in cancer cell growth.
Progression-free survival (PFS): time during and after treatment that a patient lives without cancer growing or spreading.
Duration of response (DOR): length of time a treatment keeps cancer under control after it first responds.
Objective response rate (ORR): percentage of patients whose cancer shrinks or disappears after treatment.
Disease control rate: percentage of patients who have a response or stable disease after treatment.
Additional Data From the SOHO-01 Trial
Among the 43 patients evaluable for response, the objective response rate was 72.1%, including a complete response of 2.3%, according to a previous, 2024 release from Bayer. The disease control rate was 83.7%. The median duration of response was 8.7 months, and the median progression-free survival was 7.5 months.
In a subgroup of 30 patients with HER2 YVMA insertions — the most common type of HER2 mutation in lung cancer — the response rates were even higher, with a 90% objective response rate and a 96.7% disease control rate. These patients experienced a median duration of response of 9.7 months and a median progression-free survival of 9.9 months.
In the safety population of 44 patients, most experienced treatment-related side effects. These included diarrhea (86.4%), rash (43.2%), paronychia (25%) and nausea (25%). Nearly half experienced grade 3 (severe) or higher side effects, and about one-third required dose reductions. Three patients discontinued treatment due to side effects, and 11.4% experienced serious side effects.
What is Sevabertinib?
Sevabertinib is an investigational oral treatment being studied for patients with NSCLC and other solid tumors that present with HER2-activating mutations, according to the news release from Bayer. It is a reversible tyrosine kinase inhibitor (TKI) designed to target HER2 mutations — including exon 20 insertions and point mutations — as well as EGFR, with greater selectivity for mutant over normal EGFR. Sevabertinib has not been approved for use in any country and is still under clinical evaluation. It was developed through a research collaboration between Bayer and the Broad Institute of MIT and Harvard.
In 2024, the FDA previously granted breakthrough therapy designation to sevabertinib for adults with unresectable or metastatic NSCLC that has activating HER2 mutations and whose disease has progressed following prior systemic treatment. This decision was based on early clinical findings from the SOHO-01 trial.
Breakthrough therapy designation is intended to speed the development and review of therapeutic drugs/agents which may offer substantial improvement over existing therapies for serious conditions, such as cancer, according to the FDA website. Moreover, the regulatory agency grants priority review to investigative therapies, such as those like sevabertinib, that may significantly improve the treatment, prevention or diagnosis of serious conditions.
Reference
“HER2 insertion YVMA mutant lung cancer: long natural history and response to afatinib” by Dr. Bob T. Li, et al., Lung Cancer.
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