Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.

Autor: Balinda HU; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA., Kelly WJ; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA., Kaklamani VG; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA., Lathrop KI; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA., Canola MM; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA., Ghamasaee P; Department of Neurosurgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA., Sareddy GR; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA.; Department of Obstetrics & Gynecology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA., Michalek J; Department of Population Health Sciences Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, 78229, USA., Gilbert AR; Department of Pathology and Laboratory Medicine, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA., Surapaneni P; START Center for Cancer Care, 155 E Sonterra Blvd STE. 200, San Antonio, TX, 78258, USA., Tiziani S; Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX, 78723, USA.; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, 78712, USA.; Department of Oncology, Dell Medical School, Livestrong Cancer Institutes, The University of Texas at Austin, Austin, TX, 78723, USA.; Department of Pediatrics, Dell Medical School, The University of Texas at Austin, Austin, TX, 78723, USA., Pandey R; Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX, 78723, USA.; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, 78712, USA., Chiou J; Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX, 78723, USA.; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, 78712, USA., Lodi A; Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin, Austin, TX, 78723, USA.; Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, 78712, USA., Floyd JR 2nd; Department of Neurosurgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA., Brenner AJ; Mays Cancer Center at UT Health San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA. brennera@uthscsa.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 07; Vol. 15 (1), pp. 6707. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1038/s41467-024-50558-9
Abstrakt: Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706 .
(© 2024. The Author(s).)
Databáze: MEDLINE
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