Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Aug 7;15(1):6707.
doi: 10.1038/s41467-024-50558-9.

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

Henriette U Balinda #  1 , William J Kelly #  1 , Virginia G Kaklamani  1 , Kate I Lathrop  1 , Marcela Mazo Canola  1 , Pegah Ghamasaee  2 , Gangadhara R Sareddy  1   3 , Joel Michalek  4 , Andrea R Gilbert  5 , Prathibha Surapaneni  6 , Stefano Tiziani  7   8   9   10 , Renu Pandey  7   8 , Jennifer Chiou  7   8 , Alessia Lodi  7   8 , John R Floyd 2nd  2 , Andrew J Brenner  11
Affiliations
Clinical Trial

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

Henriette U Balinda et al. Nat Commun. .

Abstract

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 .

PubMed Disclaimer

Conflict of interest statement

HB, WK, KL, PG, GS, JM, AG, PS, ST, RP, JC, AL, JF and AB have no personal, professional or financial relationships that would constitute a conflict of interest. VK and MC are on the speaker’s bureau and VK is a consultant for Gilead. Portions of this work have previously been presented in abstract form at the 2023 Society for NeuroOncology Annual Meeting, San Antonio Breast Cancer Symposium 2022 and 2024, and the European Society for Medical Oncology Virtual Congress 2020. WK and AB have received contracted funding from Gilead for a similar study.

Figures

Fig. 1
Fig. 1. Sacituzumab Govitecan (SG) inhibits tumor growth in a xenograft model of intracranial breast cancer.
Representative bioluminescent images of control and sacituzumab govitecan treated (25 mg/kg/twice weekly) mice at the start of treatment (top panels) and 2 weeks after treatment (bottom panels).
Fig. 2
Fig. 2. Overall survival for patients having breast cancer with brain metastasis after treatment with sacituzumab govitecan.
Kaplan-Meier plot showing overall survival for patients (n = 12).
Fig. 3
Fig. 3. Overall survival for patients with recurrent glioblastoma after treatment with sacituzumab govitecan.
Kaplan-Meier plot showing overall survival for patients (n = 10).
Fig. 4
Fig. 4. Best intracranial response for patients having breast cancer with brain metastasis after treatment with sacituzumab govitecan.
Waterfall plot showing best intracranial response in tumor size change from baseline for each patient (n = 8).
Fig. 5
Fig. 5. Best intracranial response for patients with recurrent glioblastoma after treatment with sacituzumab govitecan.
Waterfall plot showing best intracranial response in tumor size change from baseline for each patient (n = 7).
See this image and copyright information in PMC

References

    1. Kennecke, H. et al. Metastatic behavior of breast cancer subtypes. J. Clin. Oncol.28, 3271–3277 (2010). 10.1200/JCO.2009.25.9820 - DOI - PubMed
    1. Stupp, R. et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. Jama314, 2535–2543 (2015). 10.1001/jama.2015.16669 - DOI - PubMed
    1. Mair, M. J. et al. Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours. Nat. Rev. Clin. Oncol.20, 372–389 (2023). 10.1038/s41571-023-00756-z - DOI - PubMed
    1. Montemurro, F. et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆. Ann. Oncol.31, 1350–1358 (2020). 10.1016/j.annonc.2020.06.020 - DOI - PubMed
    1. Pérez-García, J. M. et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial. Neuro Oncol.25, 157–166 (2023). 10.1093/neuonc/noac144 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data