258TiP A phase II trial of loperamide (L) and granulocyte colony-stimulating factors (G-CSF) to improve sacituzumab govitecan (SG) tolerance in patients (pts) with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): PRIMED

SG is an antibody-drug conjugate targeting human trophoblast cell surface antigen 2 that has shown superior progression-free survival (PFS) and overall survival versus single-agent chemotherapy in pts with heavily pretreated TN and hormone receptor-positive/HER2-negative advanced breast cancer. Common adverse events (AEs) with SG include diarrhea and neutropenia, with neutropenia as the main reason for dose reduction and treatment discontinuation. We aim to evaluate prophylactic L and G-CSF to mitigate these AEs. PRIMED (NCT05520723) is a multicenter, open-label, single arm, phase II clinical trial. Selection criteria include (a) Pts aged ≥18 years with taxane-pretreated unresectable locally advanced or mTNBC; (b) At least one and up to two prior chemotherapeutic regimens for advanced disease; (c) ECOG performance status of 0-1; (d) Evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Pts will receive SG at doses of 10 mg/kg given intravenously on days 1 and 8 every 21-day cycle until disease progression, unacceptable toxicity, or patient withdrawal. L (2 mg orally twice a day or 4 mg once a day [QD], days 2, 3, 4, 9, 10, and 11) and G-CSF (0.5 MU/kg/day subcutaneously QD, days 3, 4, 10, and 11) will be administered during the first two treatment cycles. Co-primary endpoints are incidence of grade ≥2 diarrhea and grade ≥3 neutropenia after two treatment cycles. Secondary endpoints include incidence of all grade neutropenia, diarrhea, and additional AEs per NCI-CTCAE v.5.0 during the course of the study, discontinuation rate, dose reduction rate, objective response rate, clinical benefit rate, duration of response, time to response, best percentage of change from baseline in size of target tumor lesions, and PFS. Primary analysis will evaluate the rate of pts with grade ≥2 diarrhea (H0: ≥25%; H1: ≤14%) and grade ≥3 neutropenia (H0: ≥40%; H1: ≤28%). Fifty pts will be enrolled to attain 80% power. Interim analysis will assess the first 25 pts and the study will be stopped if ≥6 pts have grade ≥2 diarrhea and ≥9 pts have grade ≥3 neutropenia. NCT05520723. Medica Scientia Innovation Research (MEDSIR). Gilead Sciences.