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Current treatment options, including radiation and intrathecal chemotherapy, offer limited efficacy and are associated with significant toxicity. Generally, systemic therapy in LMD poorly penetrates the blood-brain barrier (BBB). Leveraging the L-type amino acid transporter 1 (LAT1) represents a unique therapeutic strategy, as LAT1 facilitates transport of medications across the BBB, and is also highly expressed in metastatic cancer cells. QBS72S is a first-in-class BBB-penetrant bifunctional molecule targeting overexpression of LAT1 to selectively eliminate cancer cells. It has shown preclinical efficacy in a mouse model of breast cancer LMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Phase 2a, single-arm, open-label clinical trial (NCT05305365) investigated the safety, cerebrospinal fluid (CSF) concentration, pharmacokinetics, and preliminary efficacy of QBS72S in participants with breast cancer brain metastases. Secondary endpoints included progression-free survival, overall survival, and duration of response. Correlative analyses included LAT1 immunohistochemistry and CSF cell-free RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this analysis, we report results from breast cancer participants with LMD (n\u2009=\u200910) treated with QBS72S. QBS72S was reliably detected in CSF, adequately tolerated, and two participants exhibited long-term radiographic stability or improvement lasting 6-7 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These early findings support further investigation of QBS72S as a targeted therapy for LMD, addressing an urgent unmet need in metastatic breast cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag177","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:15:35Z","timestamp":1786101335000},"source":"Crossref","is-referenced-by-count":0,"title":["Phase 2 test of QBS72S for breast cancer leptomeningeal disease"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0289-2319","authenticated-orcid":false,"given":"Seema","family":"Nagpal","sequence":"first","affiliation":[{"name":"Department of 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