Multinational phase 1-2 trial of sevabertinib in advanced HER2-mutant non-small cell lung cancer

Sevabertinib is an oral, reversible TKI with anti-HER2 activity in preclinical models. The multinational phase 1-2 SOHO-01 trial evaluated sevabertinib in patients with locally advanced or metastatic HER2-mutated NSCLC in three cohorts: cohort D comprised previously treated patients who had not received HER2-targeted therapy, patients in cohort E had previously received HER2-directed antibody-drug conjugates, and patients in cohort F had not previously received treatment. Objective response rate in the three cohorts was 64%, 38%, and 71%, respectively. Median progression-free survival was 8.3 months, 5.5 months, and not yet mature, respectively. The most common adverse event was diarrhea (grade 3 and higher in 5 to 23%). Adverse events leading to discontinuation occurred in 3%. The authors conclude that sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC.