FDA Grants Priority Review to Sevabertinib for HER2-Mutant NSCLC

Sevabertinib for HER2-Mutant NSCLC

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The FDA has granted priority review to the new drug application (NDA) seeking the approval of sevabertinib (BAY 2927088) for the treatment of adult patients with advanced non–small cell lung cancer (NSCLC) harboring HER2 mutations who have received a prior systemic therapy.1

The NDA is supported by data from the phase 1/2 SOHO-01 trial (NCT05099172), which showed that evaluable patients treated with sevabertinib at 20 mg twice per day (n = 43) experienced an overall response rate (ORR) of 72.1% (95% CI, 56.3%-84.7%), including a complete response rate of 2.3%.2 Additionally, In the overall cohort, the median duration of response (DOR) was 8.7 months (95% CI, 4.5-not estimable), and the median progression-free survival (PFS) was 8.7 months (95% CI, 4.4-12.2). Furthermore, patients harboring HER2 YVMA mutations achieved an ORR of 90.0% with a median DOR of 9.7 months and a median PFS of 9.9 months.

“Patients with HER2-mutant NSCLC are predominantly women, [and they] may be of younger age and nonsmokers. 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 health care solutions that help people living with lung cancer,” Christine Roth, executive vice president of Global Product Strategy and Commercialization and a member of the Pharmaceuticals Leadership Team at Bayer, stated in a news release.1 “If approved, sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2 activating mutation.”

Sevabertinib is an oral, small molecule TKI that previously received breakthrough therapy designation from the FDA for the treatment of adult patients with unresectable or metastatic NSCLC harboring activating HER2 mutations who have received a prior systemic therapy.

SOHO-01 was a first-in-human, open-label study that evaluated sevabertinib in patients at least 18 years of age with histologically or cytologically confirmed NSCLC that was recurrent, metastatic, or not suitable for definitive therapy and had progressed following at least 1 prior line of systemic therapy in the advanced setting.3

Patients were required to have a documented EGFR and/or HER2 mutation; measurable disease per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of at least 12 weeks; and adequate bone marrow, liver, and kidney function.

The study excluded patients with any history of primary brain or leptomeningeal disease, as well as those with the presence of symptomatic central nervous system (CNS) metastases or CNS metastases requiring local therapy. Patients with a history of congestive heart failure were also excluded.

SOHO-01 included dose-escalation, backfill, dose-expansion, and dose-extension portions. The backfill part aimed to test the doses of sevabertinib that were considered safe in the escalation part by giving the agent to more patients. This part was designed to help find optimal doses of sevabertinib that worked well and were safe to be tested in the next part. The expansion part aimed to determine the dose of sevabertinib to be tested in further studies. The extension part aimed to determine whether the selected dose of sevabertinib from the expansion part worked well.

Safety, the incidence of dose-limiting toxicities, determining the maximum tolerated dose, pharmacokinetics, and blinded independent central review–assessed ORR served as the trial’s primary end points. Secondary end points included establishing the recommended phase 2 dose, investigator-assessed ORR, DOR, disease control rate, PFS, and overall survival.

Regarding safety, 95.5% of safety-evaluable patients (n = 44) experienced treatment-related adverse effects (TRAEs); the rate of grade 3 TRAEs was 40.9%.2 The most common TRAEs included diarrhea (86.4%), rash (43.2%), and paronychia (25.0%). TRAEs led to treatment discontinuation in 6.8% of patients.

Sevabertinib is under further investigation in the phase 3 SOHO-02 trial (NCT06452277), where patients with previously untreated advanced NSCLC harboring HER2 mutations are being randomly assigned to receive sevabertinib or standard-of-care therapy.4

References

1. Sevabertinib (BAY 2927088) granted FDA priority review for the treatment of patients with HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed May 28, 2025. https://www.bayer.com/media/en-us/sevabertinib-bay-2927088-granted-fda-priority-review-for-the-treatment-of-patients-with-her2-mutant-non-small-cell-lung-cancer/
2. New results from the Investigational agent BAY 2927088 in HER2-mutant non-small cell lung cancer (NSCLC) presented at WCLC. News release. Bayer. September 9, 2024. Accessed May 28, 2025. https://www.bayer.com/media/en-us/new-results-from-the-investigational-agent-bay-2927088-in-her2-mutant-non-small-cell-lung-cancer-nsclc-presented-at-wclc/
3. First in human study of BAY2927088 in participants who have advanced non-small cell lung cancer (NSCLC) with mutations in the genes of epidermal growth factor receptor (EGFR) and/​or human epidermal growth factor receptor 2 (HER2). ClinicalTrials.gov. Updated May 13, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT05099172
4. A study to learn more about how well BAY 2927088 works and how safe it is compared with standard treatment, in participants who have advanced non-small cell lung cancer (NSCLC) with mutations in the genes of human epidermal growth factor receptor 2 (HER2) (SOHO-02). ClinicalTrials.gov. Updated April 8, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT06452277