Abstract P154: Genomic profiling and matched therapy for recurrent or metastatic salivary gland neoplasms. Results from the matched cohort of the GEMS-001 clinical trial
Authors: Hernando-Calvo Alberto , Malone Eoghan , Dai Daphne , Prawira Amy , Weinreb Ilan , Eliason Anneli , Rodriguez Angela , Lajkosz Katherine , Jennings Sarah , Spreafico Anna , Siu Lillian L. , Hansen Aaron 
Published: December 2021

Abstract
Background Salivary gland tumors (SGT) are rare and heterogeneous diseases with limited systemic options available. Results from recent basket trials including SGT cohorts for specific actionable alterations (AA) have described promising outcomes with molecularly targeted approaches (TA). Methods The GEMS-001 study (NCT02069730) is an ongoing multi-arm trial with two phases. In part 1, recurrent or metastatic (R/M) SGT patients (pts) undergo comprehensive immunohistochemistry (IHC) including HER2, androgen receptor (AR) and ALK translocation and multigene panel testing (NGS). Based on the molecular profiling results in part 1, R/M SGT pts are matched to available targeted therapies on disease progression. Here, we present the efficacy results for the matched cohort of the GEMS-001 study. Results As of July 2021, 100 pts underwent molecular profiling within part 1. According to the SGT subtype (WHO 2017): 49% adenoid cystic carcinoma (ACC), 18% salivary duct carcinoma (SDC), 9% acinic (ACI) and 24% other subtypes (O). Overall, on IHC HER2 overexpression was present in 10%, AR 24% and ALK translocation 0%. On NGS, PIK3CA mutation (mut) was in 10%, HRAS mut 7%, ERBB2/3 alterations (alt) 5%, NOTCH1-3 mut 2% and ETV6-NTRK3 fusion 2%. Up to 45% pts displayed at least 1 AA and 25% had ≥2 AA. AA were enriched in SDC (100% ≥1 AA) as compared to ACI (33% ≥1 AAs), O (58% ≥1 AA) or ACC (22% ≥1 AA) (p&lt;0.001 Fisher's exact test). A total of 34 pts (34%) were matched to proteomic or genomic alterations. Of those matched, median age was 62 years (range 47-84), M:F 26:8, 100% ECOG≤1, and their AA-TA included 15 AR (leuprolide+bicalutamide), 4 HER2 or ERBB2 alt (trastuzumab+pertuzumab), 4 PIK3CA mut (PIK3CA inhibitor), 2 cyclin pathway alt (palbociclib), 2 ETV6-NTRK3 fusion (larotrectinib) and 7 other AAs (1 EGFR L858 mut (afatinib), 1 c-KIT mut (imatinib), 1 BAP1 mut (olaparib), 1 Non-V600 BRAF mut (pan-RAF inhibitor), 1 CHEK2 mut (olaparib), 1 ATM mut (olaparib) and 1 PTCH1 (vismodegib)). As per efficacy, overall response rate was 24% and median progression free survival 6.4 months (m) (95%CI 3.4-8.9 m) for the matched population. Complete responses were observed in 2 pts treated with leuprolide+biculatamide (AR). Partial responses were observed in 2 pts treated with larotrectinib (ETV6-NTRK3), 3 pts treated with trastuzumab+pertuzumab (HER2) and 1 pt treated with leuprolide+biculatamide (AR). Notably, among responders median duration of response was 13.9 m (95%CI 4.6-18.0 m). Conclusions In our cohort, more than one third of the population were matched to TA with promising efficacy outcomes. Our results support comprehensive molecular and IHC profiling but its clinical utility may vary depending on the SGT subtype.
Citation Format: Alberto Hernando-Calvo, Eoghan Malone, Daphne Dai, Amy Prawira, Ilan Weinreb, Anneli Eliason, Angela Rodriguez, Katherine Lajkosz, Sarah Jennings, Anna Spreafico, Lillian L. Siu, Aaron Hansen. Genomic profiling and matched therapy for recurrent or metastatic salivary gland neoplasms. Results from the matched cohort of the GEMS-001 clinical trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P154.