Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer.

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• HER2 gene mutations are found in 2-4% of non-small-cell lung cancer (NSCLC) patients.
• Sevabertinib is an investigational oral tyrosine kinase inhibitor targeting HER2 with demonstrated preclinical anti-tumor effects.

Purpose of the Study:

• To evaluate the safety and efficacy of sevabertinib in patients with locally advanced or metastatic HER2-mutant NSCLC.
• To assess objective response rate, duration of response, and progression-free survival in different patient cohorts.

Main Methods:

• An open-label, multicenter, phase 1-2 study enrolled 209 patients with HER2-mutant NSCLC.
• Patients received sevabertinib 20 mg twice daily in three cohorts based on prior therapy.
• Primary endpoint was objective response rate assessed by blinded independent central review.

Main Results:

• Objective response rates were 64% (previously treated, no HER2-targeted therapy), 38% (previously treated with antibody-drug conjugates), and 71% (treatment-naïve).
• Median duration of response ranged from 8.5 to 11.0 months across cohorts.
• Grade 3 or higher adverse events occurred in 31% of patients, with diarrhea being most common (5-23% grade 3+).

Conclusions:

• Sevabertinib exhibits significant antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC.
• Diarrhea was the most common adverse event, and treatment discontinuation due to adverse events was low (3%).