437TiPCNS penetration and preliminary efficacy of sacutizumab govitecan in breast brain metastasis and glioblastoma: A surgical study

AbstractBackgroundSacituzumab govitecan (SG) is an antibody drug conjugate (ADC) that targets Trop-2 for the selective delivery of SN-38 to tumors. SG carries SN-38, a topoisomerase inhibitor active in the nanomolar range for most cells (including TNBC and GBM) and freely cross the blood brain barrier. SN-38 is conjugated to SG by a linker designated CL2A which is sensitive to acidic and conditions. SG was evaluated in a single-arm, multicenter trial with relapsed/refractory metastatic triple negative breast cancer (TNBC) with impressive results including a confirmed objective response rate of 30%, with responses occurring early (median onset of 1.9 months) and being durable (median duration 8.9m). SG has since been granted priority review designation by the FDA, with approval anticipated. Brain metastases is a significant concern in this patient population, but whether this agent is able to target the CNS through the blood brain barrier is unknown. Based upon the characteristics of this specific ADC, including the use of a pH labile linker and a payload with good CNS penetration, it is our specific hypothesis that the SG can achieve intratumoral concentrations of SN-38 sufficient to achieve therapeutic benefit in patients with neoplastic involvement of the brain. We further hypothesize that while total concentration of SN-38 will correlate with expression of trop2, free SN-38 will correlate more strongly with intratumoral hypoxia.Trial designSingle center, non-randomized, pr...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research