Oral Drug Sevabertinib Offers New Hope in Advanced Lung Cancer: A Clinical Update

Sevabertinib shows >70% objective response in HER2‑mutant NSCLC in the SOHO‑01 trial.

Sevabertinib is an oral, selective HER2-targeting agent that inhibits HER2-driven signaling in tumor cells. By focusing on mutant HER2 while minimizing wild-type EGFR activity, it addresses a mechanistic niche distinct from prior HER2 strategies such as antibody–drug conjugates and pan-HER TKIs, and it could shift outpatient sequencing toward an oral targeted option.

The trial reports an objective response rate exceeding 70% and deep tumor shrinkage in key cohorts; it also describes durable median progression-free intervals in subset analyses. The dataset documents a manageable safety profile—diarrhea is the most common adverse event and no ILD was reported. However, these findings derive from nonrandomized cohorts with limited follow-up and subgroup sizes, which constrains definitive cross-trial comparisons.

The response and safety signal places sevabertinib as a compelling addition to the HER2-directed armamentarium, though direct superiority cannot be assumed without randomized or matched analyses. To confirm durability and comparative value, future trials should look to include randomized comparisons versus standard HER2-directed therapies and enrichment by specific HER2 alterations (exon-level or insertion versus point mutations). Additionally, investigators may prospectively evaluate combination cohorts with PD-(L)1 inhibitors or chemotherapy, implement proactive ILD monitoring and diarrhea-mitigation strategies, and consider flexible dosing cohorts to optimize the efficacy–tolerability balance.