Anti-TROP2 ADC ESG401 in a master protocol clinical trial for salivary gland cancer based on molecular typing.

Abstract

6100 Background: Salivary gland carcinomas (SGC) are rare, with limited prospective clinical outcome data. There is no standard of care or FDA-approved systemic therapy for recurrent and/or metastatic (R/M) disease. Precision therapy targeting specific gene alterations is emerging as a promising approach for SGC. We designed a single-center, open-label, master protocol clinical trial evaluating the efficacy and safety of molecular subtype-guided precision neoadjuvant/transformative or rescue therapy for SGC. This report focuses on the preliminary results of the TROP2-targeted group. Methods: Pts with locally advanced/recurrent SGC received neoadjuvant/transformative therapy, while pts with locally advanced/recurrent who could not tolerate or refused surgery/radiotherapy and pts with symptomatic, rapidly progressive metastatic SGC received rescue therapy. Pts were divided into molecular subtypes (HER2, NTRK, AR, TROP2) or assigned to chemotherapy if no molecular alterations were detected. Trop2-positive pts were assigned to the TROP2 group and treated with ESG401 (16 mg/kg i.v. on days 1, 8, and 15 of each 28-day cycle). The primary endpoint was ORR per RECIST1.1; secondary endpoints included AEs, DCR, PFS, and OS. Results: As of Jan 22, 2025, 14 Trop2-positive pts were enrolled, including 4 receiving neoadjuvant/transformative therapy and 10 receiving rescue therapy. Among the 12 efficacy-evaluable pts, pathological types included salivary duct carcinoma (n=3), adenoid cystic carcinoma (n=5), and others (n=4). Safety findings were consistent with the ESG401-101 study, with no new safety signals observed. Among 4 pts receiving neoadjuvant/transformative therapy, 2 achieved decreased SD, though not meeting PR criteria. Among 8 pts receiving rescue therapy, 4 achieved PR with ORR was 50% (4/8). For 12 efficacy-evaluable pts, DCR was 100% (12/12). Three pts with brain metastases achieved IC-PR/CR, yielding an IC-ORR of 100%. Conclusions: ESG401 demonstrated promising efficacy in Trop2-positive SGC, providing a rationale for molecular subtype-based targeted therapy in this population and warranting further investigation in larger studies. Clinical trial information: NCT06145308 .