A phase II, multicenter, prospective study of sacituzumab govitecan in recurrent glioblastoma.

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 survival 1,2 . 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 .