Phase 2 trial of trastuzumab rezetecan in advanced salivary gland carcinoma in cohorts with high and low HER2 expression

Systemic treatment options for advanced salivary gland carcinoma (aSGC) are limited. A phase 2 trial at Fudan University Cancer Center (Shanghai, China) evaluated the HER2-directed antibody-drug conjugate trastuzumab rezetecan (SHR-A 1811) for aSGC in HER2-high (IHC 3+ or IHC 2+ and ISH+) and HER2-low (IHC 1+ or IHC2+/ISH-) cohorts. Trastuzumab rezetecan was administered intravenously once every 3 weeks at a recommended starting dose of 4.8 mg/kg. The primary endpoint was confirmed objective response rate (ORR). Twenty-four patients were enrolled in the HER2-high cohort and 22 in the HER2-low cohort; the median follow-up was 21.9 months and 11.3 months., respectively. The confirmed ORR was 91.7% (95% CI 73.0-99.0) in the HER2-high cohort, including four complete responses, and 45.5% (24.4-67.8) in the HER2-low cohort. Median progression-free survival and overall survival were not reached in the HER2-high cohort and were 12.7 months and 21.3 months, respectively, in the HER2-low cohort. There were no grade 5 treatment-related adverse events; grade 3 or 4 TRAEs occurred in 41.3% of patients. Interstitial lung disease occurred in 6.5%, all grade 1. The authors conclude that trastuzumab rezetecan showed high antitumor activity in HER2-high aSGC and promising activity in HER2-low aSGC, with a manageable safety profile.