Background: Treatment selection based on actionable alterations (AAs) is an appealing strategy for pts with R/M SGT. The GEMS-001 study (NCT02069730) at Princess Margaret Cancer Centre (PM) and the Vall D´Hebron Institute of Oncology (VHIO) pre-screening program facilitate the identification of AAs for R/M SGT pts and treatment selection. Methods: We analyzed R/M SGT treated at PM and VHIO from 2015 to 2020. Clinicopathological features, molecular alterations and treatment modalities were correlated with outcomes. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Clinical benefit rate (CBR) was defined by pts with partial response or stable disease ≥4 months. Clinical actionability of multigene panel testing (NGS) and immunohistochemistry (IHC) were assessed as per institutional molecular tumor boards or investigators. Pts were opportunistically matched to available therapies from each center. Results: In total 206 pts were enrolled. On IHC, HER2 overexpression was present in 9%, Androgen Receptor (AR) 33%, Estrogen/Progesterone Receptor (ER/PR) 11% and ALK overexpression 0%. On NGS, PIK3CA mutation (mut) was in 9%, NTRK fusion 6%, NOTCH1-3 mut 5%, HRAS mut 6%, ERBB2/3 alterations (alt) 4% and FGFR1-4 alt 3%. Up to 92 pts (45%) displayed at least 1 AA and 36 pts (18%) had ≥2 AAs. A total of 60 pts (29%) were matched to AAs. Of those matched, median age was 60 years (range 33-84), M:F 21:39, 95% ECOG≤1 with a median number of prior treatment lines 0 (range 0-3), and their AAs included 26 AR, 9 HER2 or ERBB2 overexpression, 9 PIK3CA mut, 3 NTRK fusion, 3 FGFR1-3 alt and 10 other AAs (2 ER/PR overexpression, 2 EGFR mut, 1 c-kit mut, 1 BAP1 mut, 1 Non-V600 BRAF mut, 1 CDKN2A mut, 1 CHEK2 mut and 1 PTCH1 mut). Overall, ORR was 27% for the matched population. See table for outcomes. Conclusions: In our cohort, almost one third of the population received therapies matched to AAs. Our results suggest that targeted therapies have promising activity in pts with R/M SGT supporting comprehensive molecular and IHC profiling in treatment determination.