265TiP SOLTI-2201 ACROSS-TROP2 trial: A phase II study to identify predictive biomarkers of sacituzumab govitecan benefit and to understand resistance mechanisms in HR+/HER2- advanced or metastatic breast cancer

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) containing a TROP2-directed antibody bound to a topoisomerase I inhibitor payload through a chemically hydrolysable CL2A linker. SG is approved for the treatment of metastatic triple-negative breast cancer (mTNBC) patients (pts) after two or more systemic therapies, including at least one of them for advanced disease; and for pts with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) who have received endocrine-based therapy (ET) and two additional systemic therapies. To date, no biomarkers, including TROP2 protein levels, have shown a clinical utility to predict TROP2-directed treatment benefit, warranting the identification of biomarkers of response to SG and the understanding of key resistance mechanisms to the drug. ACROSS-TROP2 aims to address this unmet medical need. ACROSS-TROP2 (NCT06236269) is an open-label, single arm, phase II study in pts with HR+/HER2- mBC treated with SG. It will include 50 pre- or post-menopausal female or male pts who have progressed on prior CDK4/6i plus ET and who have received up to 1 prior regimen of chemotherapy or ADC for mBC. Pts will receive SG at 10 mg/kg as an IV infusion on Days 1 and 8 of a 21-day cycle until disease progression (PD). Paired fresh biopsies before start of treatment (baseline), after 2-3 weeks of treatment (C2D1), and at PD will be collected. The primary objective is to evaluate the change in CelTIL score between baseline and C2D1 tumor samples. CelTIL, which correlates with long term efficacy outcomes, is a composite score of tumor cellularity and tumor-infiltrating lymphocytes. Secondary objectives include overall response rate, progression-free survival, duration of response, time to response, safety, and tolerability. Further correlative molecular analyses will be carried out in both tissue and blood samples collected throughout the treatment. The study will utilize a paired sample t-test to assess whether the mean change in CelTIL score is statistically different from zero. The study has been approved in Spain and is ongoing in 10 sites across SOLTI network. NCT06236269. SOLTI Cancer Research Group. Gilead Sciences, Inc.