EGFR wild-type

Zongertinib is the first oral TKI approved for HER2-mutant NSCLC and will provide patients with a convenient, tolerable and effective treatment option in an area of significant unmet need. Next steps include its potential transition to a first-line setting, identification of additional indications, and development of novel combination regimens.

In vivo studies demonstrated a 112% tumor growth inhibition in L858R-induced cancers. These findings suggest that HBE-843 holds promise as a lead compound for developing new drugs to overcome C797S mutant-mediated resistance in clinical settings.

All adverse events were manageable with appropriate supportive treatment. BAI administration of PD-1 inhibitors was associated with improved therapeutic efficacy in advanced NSCLC, yielding longer PFS and higher ORR and DCR compared to the Venous group, without increasing severe toxicity.

P=N/A, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P3, N=131, Recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

P1/2, N=120, Recruiting, Shanghai East Hospital; Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

SMARCA4 mutations conferred a poorer response for EGFR-mutant LUAD subgroups who received EGFR-TKIs. Additionally, chemotherapy plus anti-angiogenesis as first-line therapy may be more effective for Stage IV-SMARCA4 mutant LUAD with EGFR wt.

P1, N=112, Not yet recruiting, TAIBIDI PHARMACEUTICAL TECHNOLOGY(SHIJIAZHUANG) CO.,LTD.

P2, N=120, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=47, Active, not recruiting, AstraZeneca | Trial completion date: Aug 2025 --> Jan 2027 | Trial primary completion date: Aug 2025 --> Jan 2027

It received its first approval under accelerated approval in August 2025 in the USA following positive results from the Beamion LUNG-1 phase Ia/Ib trial in patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This article summarizes the milestones in the development of zongertinib leading to this first approval for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have HER2 tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.

Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates. Clinicaltrial.gov: NCT07042724.