Among the 45 patients with metastatic urothelial cancer who received treatment with sacituzumab in the phase 2 portion of a single-arm basket trial (IMMU 132-01), 14 patients achieved an objective response, for an objective response rate (ORR) of 31.1%, said Scott T. Tagawa, MD, MS, Medical Director, Genitourinary Oncology Research Program, Weill Cornell Medicine, New York, NY, at the 2019 Genitourinary Cancers Symposium.
Furthermore, the activity of sacituzumab was extended to the post–checkpoint inhibitor setting. Among the 17 patients who received previous treatment with a checkpoint inhibitor, 4 showed a response to sacituzumab, for an ORR of 23.5%.
The responses occurred “in the setting of reasonable drug tolerance,” said Dr Tagawa. The safety profile was manageable and predictable, with “a relatively low rate of discontinuations due to adverse events, none due to neutropenia.”
Trop-2 is a cell-surface antigen present on the surface of multiple types of epithelial tumors, including urothelial carcinoma, and is overexpressed in invasive tumors. Sacituzumab has a high drug-to-antibody ratio of 7 to 8 molecules of SN-38 per antibody; SN-38 is the most active metabolite of irinotecan (Camptosar).
During phase 1 of the IMMU 132-01 clinical trial conducted in patients with various types of refractory advanced epithelial malignancies, the efficacy was promising in the subset of patients with advanced urothelial carcinoma. An expansion cohort of 45 patients with urothelial cancer was therefore treated with sacituzumab, at the recommended phase 2 dosage of 10 mg/kg, given on days 1 and 8 every 21 days.
The median patient age was 67 years. The median number of previous therapies was 2, and 38% of the patients received ≥3 previous lines of therapy. A total of 17 patients had received previous treatment with a checkpoint inhibitor, 71% of whom had ≥3 lines of therapy.
The median duration of follow-up was 15.7 months; 5 patients continued treatment at the time of data cutoff, 3 of whom had ongoing responses.
Among the 14 responders, 2 (4%) had complete responses and 12 (27%) had partial responses. The majority of responses occurred early, with a median time to onset of response of 1.9 months, said Dr Tagawa. The median duration of response was 12.9 months.
The ORR was 39.3% (11 of 28) in patients receiving ≤2 previous lines of therapy and 17.6% in those receiving ≥3 previous lines. The ORR was a noteworthy 33.3% (5 of 15) among patients with liver involvement at study entry, Dr Tagawa said.
Among the overall cohort, the median progression-free survival was 7.3 months and the median overall survival was 16.3 months.
The most common treatment-emergent adverse events were diarrhea (69%), nausea (67%), fatigue (58%), and neutropenia (51%), which required at least 1 dose of granulocyte colony-stimulating factor in 24% of the patients.
“The grade 3 and 4 adverse events were largely restricted to laboratory-based adverse events, including a 38% incidence of grade 3 or 4 neutropenia, but only a 7% rate of febrile neutropenia,” said Dr Tagawa. The most frequent grade 3 or more adverse events were neutropenia and anemia (13%). In addition, 5 patients discontinued sacituzumab therapy because of potential drug-related adverse events.
The activity observed in this basket trial led to the design of the TROPHYU-01 clinical trial, an international, single-arm, open-label phase 2 study that is evaluating sacituzumab in 100 patients with urothelial cancer that progressed despite platinum-based therapy and immune checkpoint inhibition, said Dr Tagawa.
A second cohort will consist of 40 patients who cannot use platinumbased therapy and whose disease progressed after immune checkpoint therapy.