Ctni-36. sacituzumab govitecan for recurrent glioblastoma

Abstract Glioblastoma (GBM) is an aggressive and highly malignant brain tumor characterized by its infiltrative growth, rapid progression, and poor prognosis. Sacituzumab govitecan (SG), an antibody-drug conjugate, has demonstrated antitumor activity and acceptable tolerability in patients with advanced epithelial cancers. It consists of a humanized anti-Trop-2 monoclonal antibody linked to a potent topoisomerase I inhibitor, SN-38. We conducted a prospective, single center, window of opportunity trial (NCT03995706) to examine the intra-tumoral concentrations of SN-38 in patients undergoing craniotomy for recurrent GBM (rGBM; n = 12). We enrolled patients aged ≥18 years diagnosed with rGBM to receive a single intravenous dose of SG at 10 mg/kg one day before surgical resection. Tumor and corresponding serum were collected during surgery to measure their levels of SN-38. Following recovery, patients resumed SG treatment at 10 mg/kg on days 1 and 8 of 21-day cycles and were accessed for responses by MRI every third cycle using response assessment in neuro-oncology (RANO) criteria. Trop-2 and carbonic anhydrase IX (CAIX) expression was investigated by IHC. An average of 2850.6 ng/ml in serum and 128.7 ng/g in tissue of SN-38 was quantified in our patient samples. Trop-2 expression was observed in 50% of patient tumors and 38% of the samples showed high expression of hypoxia marker CAIX. A strong positive correlation between the tissue/serum SN-38 and Trop-2 (r = 0.86, p = 0.01) was observed. Median overall survival of 17.5 months (0.9 - 28.5 months) and progression free survival of 2 months (0.5 - 12 months) were observed. A multicenter, phase II clinical trial has been initiated to further investigate the efficacy of SG in patients with breast brain metastasis. Updated data on response rates and accrual to the multicenter trial for rGBM will be presented