Sacituzumab govitecan in combination with capecitabine for the treatment of advanced gastrointestinal cancers after progression on standard therapy.

TPS4271 Background: Gastrointestinal (GI) malignancies are associated with poor survival and novel therapies are urgently needed. Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) that targets the tumor-associated antigen Trop-2 (trophoblast cell-surface antigen 2). SG is covalently bound to the topoisomerase I inhibitor SN-38, which is the active metabolite of irinotecan. Trop-2 is overexpressed in most GI malignancies, including colorectal, gastric, and pancreatic cancers, and is associated with poor prognosis. SG has been approved for the treatment of second-line triple-negative breast cancer and pre-treated hormone-receptor positive metastatic breast cancer but its role in GI cancers is not determined. Furthermore, its combination with capecitabine has never been studied. Methods: We are conducting a single arm, single institution, dose escalation phase 1 trial with a 3+3 design of combination SG plus capecitabine. SG dosing will be at three levels: Level -1 at 5mg/kg; Level 0 at 7.5mg/kg; and Level +1 at 10mg/kg. Dosing will start at dose level 0. SG will be administered as an intravenous infusion on Days 1 and 8 of a 21-day cycle. Capecitabine dose is fixed at 825mg/m 2 and will be delivered orally twice a day for 14 days on and 7 days off, starting on Day 1, of the 21-day cycle. Key eligibility criteria include histologically documented metastatic adenocarcinoma of GI origin, including gastroesophageal, colorectal, and pancreaticobiliary, that has failed standard therapy; age ≥18years; ECOG performance status 0-1; and adequate end organ function. Key exclusion criteria include previous receipt of topoisomerase 1 inhibitors. The primary endpoint is the Recommended Phase 2 Dose (RP2D). Secondary endpoints include objective response rates, duration of response, progression-free and overall survival. An exploratory endpoint is the correlation between Trop-2 expression in collected archival tissue and clinical outcomes. Optional biopsies will be offered for patients with missing or insufficient archival tissue. This study has been registered under NCT06065371 and is actively enrolling. The trial will enroll up to 20 patients. The trial is funded by Gilead Sciences, Inc. Clinical trial information: NCT06065371 .