Background: Pts with advanced/metastatic EC who progressed on or after platinum (PT)-based and anti–PD-(L)1 therapies have a poor prognosis with limited treatment options. SG is a Trop-2–directed antibody-drug conjugate. In the open-label, phase 1/2 IMMU-132-01 basket study, SG monotherapy resulted in a 22% objective response rate (ORR) with a manageable safety profile in 18 pts with metastatic EC who had relapsed after or were refractory to ≥1 prior standard therapeutic regimen (Bardia et al. Ann Oncol. 2021). Here, we report early data in pts with advanced/ metastatic disease from the EC cohort of the TROPiCS-03 Ph2 study. Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, Ph 2 basket study in pts with metastatic solid tumors. Adult pts in the EC cohort progressed after prior PT-based chemotherapy and anti–PD-(L)1 directed therapy [requirement for PD-(L)1 progression added in amendment], had ECOG PS 0-1 and creatinine clearance ≥30 mL/min. Pts received 10 mg/kg of SG on D1 and D8 of a 21-D cycle. The primary endpoint was ORR by investigator’s assessment per RECIST 1.1. Secondary endpoints included duration of response (DOR), clinical benefit rate (CBR), and progression-free survival (PFS) per investigator’s assessment, overall survival, and safety. The safety population included pts who received ≥1 dose of SG; the efficacy population included pts receiving ≥1 dose of SG and had ≥13 weeks of follow-up. Results: As of data extraction on October 11, 2022, 28 pts received ≥1 dose of SG. Median study follow-up was 5.3 mo (range, 0.4-13.1); median age 69 y (range, 44-83), 57% ECOG PS 1,14% microsatellite instability high. Pts received a median of 3 prior therapies (range, 1-6); 100% received prior PT-based chemotherapy, 61% prior immunotherapy, 54% prior targeted agents, and 11% prior hormonal therapy. In 20 pts with ≥13 weeks of follow-up, ORR was 25% (95% CI, 8.7-49.1). Regarding best overall response, all responses were partial response (PR). In addition, stable disease (SD) was 40% and progressive disease was 15%; CBR (confirmed complete response + PR + SD ≥ 6 mo) was 35% (95% CI, 15.4-59.2). Median PFS was 5.6 mo (95% CI, 2.3 mo-not reached [NR]) and median DOR was NR (95% CI, 2.76 mo-NR; n = 5). Treatment was ongoing for 50% of pts. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 64% of pts; most common grade ≥3 TRAEs were neutropenia (25%), febrile neutropenia (14%), and diarrhea (14%). Discontinuation rate due to TRAEs was 7%. While on treatment, two deaths occurred due to causes unrelated to SG. Conclusions: Preliminary findings showed encouraging efficacy of SG with a manageable toxicity profile in a pretreated population with advanced/metastatic EC. Safety signals were consistent with the known SG safety profile. This early analysis will be updated with the full dataset. Clinical trial information: NCT03964727.