VJToday

FDA approves sevabertinib (BAY 2927088) for HER2-mutant non-small cell lung cancer

On November 19, 2025, the U.S. Food and Drug Administration (FDA) approved sevabertinib, an oral, reversible HER2 tyrosine kinase inhibitor (TKI), for adult patients within HER2-mutant non-squamous non-small cell lung cancer (NSCLC).1 NSCLC harboring HER2 (ERBB2) mutations represents a small but aggressive molecular subset, with trastuzumab deruxtecan and zongertinib being the only FDA-approved agents approved to patients. However, unlike other NSCLC subtypes, HER2-mutant NSCLC lacks a robust, well-established treatment regimen.2,3

The approval of this agent is based on clinical evidence from the Phase I/II SOHO-01 trial (NCT05099172), a multi-cohort, open-label, single-arm trial which assessed sevabertinib in patients with advanced NSCLC who have a HER2-activating mutation. The primary endpoint was objective response rate (ORR), and secondary endpoints were duration of response (DOR) and progression-free survival (PFS).1,4

An ORR of 71% (95% CI: 59, 82) and a median DOR of 9.2 months (95% CI: 6.3, 15.0) were reported amongst the 70 patients who previously received systemic therapy and were naïve to HER2-targeted therapy. Additionally, a DOR of six or more months was reported in 54% of responding patients. Among 52 patients who progressed on systemic therapy, including HER2-targeted antibody drug conjugates, an ORR of 38% (95% CI: 25, 53) and a median DOR of 7.0 months (95% CI: 5.6, not evaluable) were achieved, with 60% of responding patients having a DOR of six or more months.1

We recently spoke with Xiuning Le, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, who gave an overview of the trial data and its significance, stating that,

“There is a clear and unmet need that we need a small molecule inhibitor for this patient population … overall this drug has showed safety toxicity profile to be quite manageable and this time we’re reporting really good clinical efficacy data”

The approval of sevabertinib marks an important advance in addressing the critical unmet need for targeted therapies in HER2-mutant NSCLC. This could provide patients with a well-tolerated, oral option and redefine the therapeutic landscape in this molecular subset.

References:

  1. Center for Drug Evaluation and Research. FDA approves cemiplimab-rwlc [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Oct 19]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
  2. Aliaga PT, Spitaleri G, Ilaria Attili, Corvaja C, Battaiotto E, Angelopoulos PA, et al. HER2 in Non-Small Cell Lung Cancer (NSCLC): Evolution of the Therapeutic Landscape and Emerging Drugs—A Long Way to the Top. Molecules. 2025 Jun 18;30(12):2645–5.
  3. Center for Drug Evaluation and Research. FDA approves cemiplimab-rwlc [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Oct 19]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations
  4. Le X, Kim TM, Loong HH, Arsela Prelaj, Goh BC, Li L, et al. Sevabertinib in Advanced HER2 -Mutant Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2025 Oct 17

Written by Henry Shippey

Edited by Calum Lang