Trastuzumab Deruxtecan in Advanced Solid Tumors With Human Epidermal Growth Factor Receptor 2 Amplification Identified by Plasma Cell-Free DNA Testing: A Multicenter, Single-Arm, Phase II Basket Trial.

PURPOSE

HERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 ()-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing.

PATIENTS AND METHODS

Patients exhibited advanced solid tumors with amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity.

RESULTS

Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including -mutant colorectal (1/3), -mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma CN above versus below the baseline median value did not differ for impact response; however, clearance of amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease.

CONCLUSION

T-DXd treatment demonstrated high ORR with durable response in patients with advanced -amplified solid tumors determined with cfDNA testing.