SHR-A1811 in HER2-expressing salivary gland cancers: Preliminary efficacy and safety results.

Abstract

6006 Background: Salivary gland cancer (SGC) is a rare and heterogeneous malignancy with limited treatment options in advanced stages. Overexpression of human epidermal growth factor receptor 2 (HER2) is linked to aggressive histological subtypes and poor prognosis in SGC, making HER2 a promising target for precision therapy. This study evaluates the efficacy and safety of SHR-A1811, a HER2-targeted antibody-drug conjugate (HER2-ADC), in patients with advanced SGC through a molecular subtype-guided approach (NCT05924256). Methods: Patients with advanced SGC were stratified into four arms based on genetic subtypes. This analysis focuses on Arm 1 (HER2 overexpression: IHC 3+ or IHC 2+/ISH+) and Arm 4 (HER2-low: IHC 1+ or IHC 2+/ISH-). In Arm 1, patients received SHR-A1811 at 4.8 mg/kg IV on Day 1 of a 21-day cycle. In Arm 4, patients received 4.8 mg/kg or 5.6 mg/kg (if tolerated). The study followed Simon’s two-stage design, with the primary endpoint of objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of January 1, 2025, 33 patients were enrolled (baseline characteristics in Table 1). In Arm 1 (21 evaluable patients), the ORR was 85.7%, and the DCR was 100%. In Arm 4 (10 evaluable patients), the ORR was 30.0%, and the DCR was 100%. After a median follow-up of 9.9 months (range: 1.2–16.6) for Arm 1 and 6.0 months (range: 4.7–9.2) for Arm 4, neither median OS nor PFS was reached. Only one patient in Arm 4 experienced disease progression. Treatment-related adverse events (TRAEs) occurred in 32 patients (97%). The most common grade 3/4 TRAEs included neutropenia (36%), leukopenia (15%), anemia (12%), and lymphopenia (12%). Two patients (6%) experienced treatment-related serious adverse events (SAEs), and one patient (3%) developed grade 1 interstitial lung disease. No patient discontinued treatment due to TRAEs, and no treatment-related deaths were reported. Conclusions: SHR-A1811 demonstrated promising efficacy in both HER2-positive and HER2-low advanced salivary gland cancers, achieving high ORRs and DCRs with an acceptable toxicity profile. Clinical trial information: NCT05924256 . Baseline characteristics. Arm 1（N=23） Arm 4（N=10） Age (years), Median (range) 58 (26-75) 56 (36-66) Male : Female 16:7 8:2 HER2 status, n (%) IHC 3+, 19 (83)IHC 2+/ISH+, 4(17) IHC 1+, 8(80)IHC 2+/ISH-, 2(20) Histology Salivary duct carcinoma, n (%) 12 (52) 1 (10) Carcinoma ex pleomorphic adenoma, n (%) 3 (13) 2 (20) Adenoid cystic carcinoma, n (%) 0 2 (20) Others, n (%) 8 (35) 5 (50) Prior treated for patients, n (%) 16 (70) 9(90) Prior systemic therapy lines, Median (range) 0 (0-3) 1 (0-7) Anti-HER2 treatment, n (%) 5 (22) 0