KEY TAKEAWAYS
- The Early Phase 1 trial aimed to assess intra-tumoral concentrations and intracranial efficacy of SG in patients with BCBM and rGBM.
- The primary endpoints were to determine Median Total SN-38 Levels & Biomarker Analysis.
- SG is well-tolerated, penetrates intracranial tumors well, and shows promising CNS activity.
Sacituzumab Govitecan (SG) is an antibody-drug combination that targets epithelial cancers expressing TROP-2. It has shown promise in animal studies, specifically in breast cancer, by stopping tumor growth and improving mice’s survival.
Henriette U. Balinda and the team aimed to assess intra-tumoral concentrations and intracranial efficacy of SG within tumors and its effectiveness in the brain in patients with breast cancer and brain metastases (BCBM) or recurrent glioblastoma (rGBM) undergoing craniotomy.
Researchers conducted this window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio. They involved 25 patients with BCBM or rGBM, aged 18 or older. All participants received a single dose of SG at 10 mg/kg intravenously 1 day before their surgery, and then continued with additional doses on days 1 and 8 of 21-day cycles after they recovered from the surgery.
The results indicated that progression-free survival (PFS) was 8 months for the BCBM group and 2 months for the rGBM group. Overall Survival (OS) was 35.2 months for patients with BCBM and 9.5 months for those with rGBM. Grade ≥3 adverse events (AEs) included neutropenia (28%), hypokalemia (8%), seizures (8%), thromboembolic events (8%), urinary tract infections (8%), and muscle weakness (8%).
Median SN-38 levels in post-surgical tissue were 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, meeting the primary endpoint. Biomarker analysis showed direct payload delivery and no effect from hypoxic changes. The Objective Response Rate (ORR) was 38% for BCBM and 29% for rGBM, with Trop-2 expression found in 100% of BCBM and 78% of rGBM tumors.
The study concluded that SG was well tolerated, showed good penetration into intracranial tumors, and demonstrated promising preliminary activity within the CNS.
The study was sponsored by Gilead.
Source: https://pubmed.ncbi.nlm.nih.gov/39112464/
Clinical trial: https://clinicaltrials.gov/study/NCT03995706
Balinda HU, Kelly WJ, Kaklamani VG, et al. (2024). “Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.” Nat Commun. 2024 Aug 7;15(1):6707. doi: 10.1038/s41467-024-50558-9. PMID: 39112464.
