On 18 October 2025 at the European Society of Medical Oncology, held in Berlin, Germany, from 17 to 21 October, two important datasets were read out in first-line metastatic non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) activating mutations. This subtype represents between 2% and 4% of NSCLC patients. Outcomes are generally suboptimal for HER2-mutant disease for patients with these driver mutations who do not respond well to the current immunotherapy-based standard of Merck and Co’s Keytruda (pembrolizumab) with or without chemotherapy, and this has created a significant unmet need. Enhertu (trastuzumab deruxtecan) is currently approved after prior systemic therapy in HER2-mutant NSCLC and is commonly used in the second line.
The first trial presented in Berlin was the Phase I/II SOHO-01 trial which evaluated Bayer’s sevabertinib, a HER2 targeting tyrosine kinase inhibitor (TKI). In the treatment-naïve cohort (Cohort F) , the objective response rate (ORR) was 71% and the disease control rate (DCR) 89%. Median progression-free survival (PFS) was not yet estimable; however, 12-month PFS was 55%. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 21% of patients. Diarrhoea was the most common side effect, affecting 87% of patients at any grade, although these events were generally low-grade and did not result in any treatment discontinuations
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Following SOHO-01, the Phase I Beamion Lung-1 study investigated Boehringer Ingelheim’s Hernexeos (zongertinib), a HER2-selective TKI, in the same population of treatment-naïve patients with HER2-activating mutations. In this trial, the ORR was 77% and the DCR 96%. As with sevabertinib, median PFS was not yet estimable, though the 6-month PFS rate was 79%. Grade 3 or higher TRAEs were observed in 18% of patients, and 54% experienced diarrhoea of any grade, again predominantly low grade and manageable with supportive care.
Bayer and BI have reported broadly similar efficacy outcomes for sevabertinib and Hernexeos in HER2-mutant NSCLC. However Hernexeos appears to have a more favourable tolerability profile, particularly with respect to diarrhoea. Following its accelerated approval in the second-line HER2-mutant NSCLC setting in September 2025, Hernexeos is likely to benefit from increased physician familiarity with its safery and efficacy profile, which could translate into greater uptake.s becoming more familiar with the efficacy and safety profile increasing its prescriptions. According to GlobalData’s Non-small Cell Lung Cancer: Seven-Market Drug Forecast and Market Analysis, Hernexeos is projected to achieve $54 million in sales across the seven major markets (7MM: France, Germany, Italy, Japan, Spain, the UK and the US) by 2032 compared with $49 million for sevabertinib. The competition between the two agents is expected to remain fierce, but given the relatively small size of the HER2-mutant NSCLC population, the market is unlikely to sustain two major long-term competitors.
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By GlobalData
