ESMO Virtual Congress 2020: TROPHY-U-01 Cohort 1 Final Results: A Phase 2 Study of Sacituzumab Govitecan (SG) in Metastatic Urothelial Cancer That Has Progressed After Platinum and Checkpoint Inhibitors

( Treatment options for advanced urothelial cancer that has progressed through platinum chemotherapy and immune checkpoint blockade consist of (1) single agent chemotherapy, (2) FGFR inhibitor therapyfor tumors harboring susceptible alterations, and (3) the antibody-drug conjugate enfortumab vedotin.

Sacituzumab govitecan is an antibody-drug conjugate containing an antibody against the epithelial cell surface molecule Trop-2 that is attached to a chemotherapy payload of SN-38 (a potent derivative of irinotecan). This drug does not require internalization into tumor cells to deliver its payload, and is notable for a high drug-to-antibody ratio amongst antibody-drug conjugates. Clinical data from the urothelial carcinoma cohort of IMMU-132-01 revealed a 31% overall response rate (ORR) with this agent. In this presentation, Yohann Loriot, MD, MSc presented data from cohort 1 of the TROPHY-U-01 study involving the treatment of 113 patients with metastatic urothelial carcinoma that progressed on prior platinum and immune checkpoint therapy. Interim analysis from this cohort was previously presented at the European Society of Medical Oncology (ESMO) 2019 meeting, suggesting an ORR rate of 29% in the 35 patients analyzed at that point.

The study design is shown below. The drug is administered at a dose of 10 mg/kg on days 1 and 8 or a 21-day cycle. The primary objective of this study was the objective response rate, with a null hypothesis of ORR <= 12%.


As of the data cut-off of May 18, 2020, 16 of the 113 patients evaluated were continuing on treatment. Two-thirds of patients had discontinued therapy due to progressive disease, and three patients discontinued therapy because they passed away. The median age of the cohort was 66, and the median number of prior anticancer therapies was 3.


The trial met its primary endpoint with an objective response rate of 27% (31 patients). There were 6 complete responses. The median duration of response was 5.9 months, and the median time to onset of response was 1.6 months. 76% of patients showed reductions in tumor size on treatment. The clinical course of the 31 responders are shown below.


The median progression-free survival in this cohort was 5.4 months, and the median overall survival was 10.5 months.

The most common treatment-related adverse event was diarrhea, with 9% of patients have a grade 3 event, consistent with what might be expected from an irinotecan-derived drug. Neutropenia occurred in 46% of patients.


These results confirm the clinical activity of sacituzumab govitecan in heavily pre-treated metastatic urothelial carcinoma patients who progressed on platinum and immune checkpoint blockade therapy. The ORR of 27% compares favorably to single-agent chemotherapy in this pre-treated setting (10%, PFS 2-3 months). Importantly, in the Q&A setting, Dr. Loriot reported that 10 patients in this cohort was previously treated with enfortumab vedotin. Of these 10 patients, 3 had a partial response including 2 patients whose disease had progressed on enfortumab.

The phase 3 confirmatory trial of sacituzumab in urothelial carcinoma is underway (TROPiCS-04, NCT04527991). The schema for that trial is shown below. 


Presented by: Yohann Loriot, MD, MSc, Department of Cancer Medicine, INSERM U981, Villejuif, France

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020.