Multcenter phase 2 trial of trastuzumab deruxtecan for advanced solid tumors with HER2 amplification identified by plasma cell-free DNA testing

The multicenter phase 2 HERALD/EPOC 1806 trial in Japan evaluated the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors with HER2 amplification detected by cell-free DNA (cfDNA) testing. The study includeded 62 patients with 16 cancer types and a median baseline plasma HER2 copy number (CN) of 8.55 (range 2.4-73.9). The confirmed overall response rate was 56.5% (95% CI 43.3-69.0), with responses in among others 1 of 3 KRAS mutant colorectal cancers, 5 of 6 PIK3CA mutant endometrial cancers, and 1 of 2 tissue HER2-negative gastric cancers. Clearance of HER2 amplification on cycle 2 day 1 was associated with higher response values compared with persistence. Median progression-free survival was 7.0 months (95% CI 4.9-9.7) and median duration of response was 8.8 months (5.8-11.2). The majority of toxicities were mild to moderate, with grad3 interstitial lung disease in one patient. The authors conclude that T-DXd demonstrated high ORR with durable response in patients with advanced HER2-amplified solid tumors identified with cfDNA testing.