Ahmet Dirican: Is a New Agent Emerging for Metastatic Urothelial Carcinoma in the 2L+ Setting?

Ahmet Dirican, Professor of Medical Oncology at Medicana International İzmir Hospital, shared a post on X:

“Is a new agent emerging for metastatic urothelial carcinoma in the 2L+ setting?

Sacituzumab tirumotecan (sac-TMT) – a next-generation TROP2-directed ADC – shows promising activity after platinum chemotherapy and immune checkpoint inhibitors.

Phase 1/2 Cohort 9 results: 

• ORR: 31%
• DCR: 71%
• Median PFS: 5.5 months
• Median OS: 12.1 months
• Duration of response: Not reached
• 12-month sustained response: 53%

IHC TROP2 analysis:

• High expression: 69%
• ORR: 32%
• Low expression: 10% (Low-TROP2 sample size too small for robust response correlation)

A notable signal of antitumor activity in a heavily pretreated population.

TROP2 ADC cross-trial landscape. How does sacituzumab tirumotecan fit among other TROP2-targeted ADCs?

• Sacituzumab tirumotecan ORR: 31%    Median PFS: 5.5 mo
• Sacituzumab govitecan (Phase 3) ORR: 23%    No OS benefit vs chemotherapy
• Datopotamab deruxtecan ORR: ~25%    Median PFS: 6.9 mo

Together, these data reinforce TROP2 as a clinically relevant therapeutic target in urothelial carcinoma. Cross-trial comparison – interpret cautiously.

Title: Sacituzumab tirumotecan in participants with advanced or metastatic urothelial carcinoma and disease progression after chemotherapy and immune checkpoint inhibitors

Authors: Y. Zhu, S. Jiang, Y. Shi, S. Wang, F. Yuan, F. Zhou, K. Jiang, X. Zhang, L. Seneviratne, G. Yu, M. Zhang, T. Liu, X. Li, X. Chen, X. Wang, S. Zhang, Y. Liu, Y. Ge, M. Chen, G. Blumenthal, O. Akala, Y. Li, X. Li, J. Ge, D. Ye

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