Authors: William Kelly, Christine Cordova, Brian D. Vaillant, Henriette Balinda, Joel Michalek, Andrea Gilbert, John Floyd, Andrew J. Brenner
Published: 2024-07-11
DOI: 10.1200/jco.2024.42.16_suppl.tps2094
Source: Full article
TPS2094 Background: Despite decades of research, glioblastoma (GBM) remains the most common and aggressive primary brain malignancy. GBM has been shown to express trophoblast cell-surface antigen 2 (Trop2) and this expression corelates with proliferation rate, micro vessel density, histological grade and clinical survival1,2. Antibody drug conjugates (ADC) targeting cell surface receptors have been recently shown to produce intracranial response rates of 25-44%%3-5. Sacituzumab Govitecan (SG) consists of an ADC targeting Trop2 attached via linker to a chemotherapy payload, SN-38. In 2020, it received FDA approved for the treatment of metastatic triple-negative breast cancer followed by HR+/HER2- metastatic breast cancer in 2023. Methods: This is a multi-center, open-label, prospective, single-arm phase 2 study using a 2-stage adaptive Bayesian design. Patients with GBM (IDH wild-type), recurrent following standard-of-care chemoradiation, received SG at 10mg/kg IV on days 1 and 8 of a 21 day cycle. Patients were assessed by RANO and CTCAE v5. The primary endpoint was progression-free survival of patients on SG as compared to a historical control of lomustine monotherapy. Enrollment was conducted at UT Health Science Center in San Antonio, Cleveland Clinic and Texas Oncology in Austin. A total of 23 patients have been screened with 3 screen failures and 20 patients enrolled. The study has now entered interim analysis. Trial Registration: This trial (NCT04559230) is enrolled at Clinical Trials.gov as “Sacituzumab Govitecan in Recurrent Glioblastoma”: https://clinicaltrials.gov/study/NCT04559230 Funding: WK and AB have received contracted funding from Gilead. Additional support provided by an NCI Cancer Center Support Grant (P30CA016672) and an Early Clinical Investigator Award through CPRIT (RP210164). References: 1. Ning, S., et al., TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas. Neurol Sci, 2013. 34(10): p. 1745-50; 2. Harvard, B.I.o.M.a., Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNA expression and clinical features; 3.Fabi, A., et al., T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer. Breast, 2018.41: p. 137-143; 4. Jacot, W., et al., Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat, 2016. 157(2): p. 307-318. Clinical trial information: NCT04559230 .