Dr Kelly on Early Efficacy Signals and Safety With Sacituzumab Govitecan in Recurrent Glioblastoma

"We did a post hoc analysis looking to see if OS correlated with TROP2 expression, and found that there was a statistically significant correlation between OS and TROP2 expression we measured in a way called an H-score. We’re very excited about that potential survival signal."

William Kelly, MD, a medical oncologist specializing in neuro-oncology and thoracic oncology at the University of Texas Health San Antonio MD Anderson Cancer Center and an assistant professor in the Division of Hematology and Oncology at the Mays Cancer Center, discusses key efficacy findings from both an interim analysis and a post-hoc analysis of a phase 2 study (NCT04559230) evaluating sacituzumab govitecan-hziy (Trodelvy) in patients with recurrent glioblastoma.

The multicenter, open-label, single-arm study evaluated sacituzumab govitecan in patients with recurrent, IDH wild-type glioblastoma following standard-of-care chemoradiation. Sacituzumab govitecan is an antibody-drug conjugate (ADC) targeting TROP2 with an SN-38 chemotherapy payload, Kelly explained.

Findings from an interim analysis of the study were presented at the 2024 Society for Neuro-Oncology Annual Meeting and demonstrated that sacituzumab govitecan was well tolerated and showed preliminary clinical activity in this patient population, Kelly shared. Among the first 20 patients enrolled onto the study, 52% expressed TROP2 (H-Score ≥ 100; mean, 123.6 ± 90 [range, 0-248]) Kelly explained. The mean overall survival (OS) was 7.0 months, and the mean progression-free survival was 2.0 months, he reported.

Given the variability in treatment response and based on prior signals from the phase 0 portion of the study, a post hoc analysis was conducted to explore whether TROP2 expression correlated with OS, Kelly detailed. Using an accelerated failure time model, results showed a statistically significant association between higher TROP2 expression among 19 evaluable patients—measured via H-score—and improved survival outcomes (P = .0123), Kelly stated.

These results suggest a potential survival signal in patients whose tumors exhibit elevated TROP2 expression, supporting the need for further investigation into TROP2 as a predictive biomarker, Kelly said. Future research may focus on refining patient selection criteria and optimizing therapeutic strategies for this challenging-to-manage disease, Kelly concluded.