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Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced
Yohann Loriot1, Arjun V Balar2, Daniel P Petrylak3
1Institut de Cancérologie Gustave Roussy, Villejuif, France.
Purpose:
Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression.
Patients And Methods:
TROPHY-U-01 (NCT03547973) is an open-label phase II study that assessed the efficacy and safety of SG (alone or in combinations) in patients with unresectable locally advanced or metastatic UC (mUC). Archival tumor samples collected at enrollment for C1-3 were analyzed for Trop-2 membrane expression by considering histological scores (H-scores; scale 0-300) and the percentage of membrane positive tumor cells at low magnification (4×). The association of Trop-2 with clinical endpoints [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] was evaluated.
Results:
In C1-3, tissue was collected from 158 (82%) of 192 treated patients, and 146 (76%) had evaluable Trop-2 data. Trop-2 was highly expressed in tumor samples. The median [interquartile range (IQR)] Trop-2 H-score was 215 (180-246), and the median (IQR) percentage of membrane positive tumor cells was 91% (80-98). Trop-2 expression at any level was observed in 98% of patients. Furthermore, ORR, PFS, and OS benefits were observed across all Trop-2 expression levels.
Conclusions:
Trop-2 protein is highly expressed in UC, as confirmed by examining tumors from patients enrolled in the TROPHY-U-01 trial. The results indicate that SG demonstrates efficacy in mUC across Trop-2 expression levels.
Insights
Sacituzumab govitecan (SG) effectively treats metastatic urothelial cancer (mUC) by targeting Trop-2. This study confirmed high Trop-2 expression in mUC tumors, showing SG
Area of Science:
- Oncology
- Translational Research
- Biomarker Analysis
Background:
- Human trophoblast cell surface antigen 2 (Trop-2) is a protein frequently overexpressed in urothelial cancer (UC).
- Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, delivering a potent payload for cancer therapy.
- Understanding Trop-2 expression is crucial for evaluating the efficacy of Trop-2-targeted therapies like SG in UC.
Purpose of the Study:
- To investigate Trop-2 protein expression levels in urothelial cancer (UC) tumors from patients treated with Sacituzumab govitecan (SG).
- To assess the association between Trop-2 expression and the clinical efficacy of SG in patients with metastatic UC (mUC).
- To analyze Trop-2 expression in tumor samples from cohorts 1 to 3 of the TROPHY-U-01 study.
Main Methods:
- Analysis of archival tumor samples from 146 patients with evaluable Trop-2 data in the TROPHY-U-01 phase II study.
- Trop-2 membrane expression was quantified using histological scores (H-scores) and the percentage of membrane-positive tumor cells.
- Correlation of Trop-2 expression levels with clinical endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- Trop-2 was highly expressed in the majority of UC tumors analyzed, with 98% of patients showing expression at some level.
- The median Trop-2 H-score was 215, and the median percentage of membrane-positive tumor cells was 91%.
- Significant clinical benefits, including ORR, PFS, and OS, were observed across all evaluated levels of Trop-2 expression.
Conclusions:
- Trop-2 protein is consistently highly expressed in urothelial cancer (UC) tumors.
- Sacituzumab govitecan (SG) demonstrates efficacy in treating metastatic UC (mUC) irrespective of Trop-2 expression levels.
- Trop-2 expression is a validated target for SG therapy in mUC.
