Bayer today announced that the investigational compound sevabertinib (BAY 2927088) has been granted Priority Review status by the US Food and Drug Administration (FDA) for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2/ERBB2) mutations and who have received a prior systemic therapy. Sevabertinib is an oral, small molecule, tyrosine kinase inhibitor (TKI).

“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 validates both the unmet need and the potential for sevabertinib to fulfill that need,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. “If approved, sevabertinib will help address critical unmet needs and improve outcomes for these patients, who currently have a poor prognosis and limited treatment options.”

The regulatory application for sevabertinib is based on positive results from the ongoing Phase I/II SOHO-01 trial in patients with advanced NSCLC harboring a HER2-activating mutation, with disease progression after ≥1 systemic therapies for advanced disease, and who were naïve to treatment with a HER2-targeted TKI.

The Breakthrough Therapy designation for sevabertinib was supported by preliminary clinical evidence from the SOHO-01 trial. A Breakthrough Therapy designation is specifically designed to expedite the development and review of investigational medicines that have the potential to provide substantial improvement over available therapies in areas of high unmet medical need. By expediting the development and review process via a Breakthrough Therapy designation, promising therapies can be made available to patients as quickly and as safely as possible.

Results from SOHO-01 (NCT05099172)[2]

SOHO-01 is an ongoing, open-label, multicenter Phase I/II study. The latest results are from two expansion cohorts; patients with advanced NSCLC with HER2-activating mutations who had disease progression after ≥1 systemic therapies and were either naïve to HER2-targeted therapy (Cohort D) or previously treated with HER2-targeted antibody-drug conjugates (Cohort E). Both cohorts received oral sevabertinib 20 mg twice daily.

As of October 14, 2024, 44 patients from cohort D and 34 patients from cohort E were treated. The investigator-assessed objective response rate was 70.5% (95% CI 54.8, 83.2) in D and 35.3% (95% CI 19.7, 53.5) in E. The disease control rates (response or stable disease for ≥12 weeks) were 81.8% (D) and 52.9% (E). Median duration of response (DOR) was 8.7 months (95% CI 4.5, not estimable [NE]) in D and 9.5 months (95% CI 4.1, NE) in E.

The safety profile of sevabertinib was found to be manageable, and consistent with previous reports. Treatment-related adverse events (TRAEs) were reported in 97.4% of patients; diarrhea was the most common TRAE leading to dose reduction, but no patients discontinued treatment due to diarrhea. There were no cases of interstitial lung disease.

Sevabertinib is an investigational agent and has not been approved by any health authority for use in any country, for any indication. It is currently being evaluated as a potential new targeted treatment option for patients with NSCLC harboring human epidermal growth factor receptors 2 (HER2) activating mutations. The ongoing Phase III SOHO-02 trial (NCT 06452277) is evaluating BAY 2927088 as a first-line treatment option for these patients. Sevabertinib is also being studied in patients with metastatic or unresectable solid tumors harboring HER2-activating mutations (panSOHO), excluding advanced non-small cell lung cancer (NSCLC). Sevabertinib is an oral, reversible tyrosine kinase inhibitor (TKI) that potently inhibits mutant HER2, including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with high selectivity for mutant vs wild-type EGFR. Investigational agent sevabertinib is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer, accounting for more than 85% of cases. Activating HER2 mutations are found in 2% to 4% of advanced NSCLC. 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes it more difficult to treat. Patients with HER2-mutant NSCLC currently face limited treatment options, highlighting an urgent need for more effective therapies.

Source: bayer.com