medwireNews: Initial results from the phase II TROPHY-U-01 trial confirm the antitumor activity of sacituzumab govitecan in patients with metastatic urothelial carcinoma that has progressed after platinum chemotherapy or checkpoint inhibition.
The treatment had no unexpected toxicity and “has the potential to change the treatment landscape of urothelial carcinoma,” Scott Tagawa (Weill Cornell Medicine, New York, USA) told delegates at the ESMO Congress 2019 in Barcelona, Spain.
Tagawa explained that sacituzumab govitecan is an antibody–drug conjugate that targets Trop-2, an epithelial surface antigen highly expressed in urothelial carcinoma. The drug element, SN-38, is a metabolite of the topoisomerase I inhibitor irinotecan and is more potent than the parent compound. It is released from the anti-Trop-2 antibody via intracellular linker hydrolysis and has previously shown antitumor activity across a number of tumor types, he said.
After a median 4.1 months of follow-up, the objective response rate (ORR) to sacituzumab govitecan 10 mg/kg, given on days 1 and 8 of each 21-day cycle, was 29% among 35 patients with metastatic urothelial carcinoma after a median of three prior platinum chemotherapy or checkpoint inhibition regimens.
Tagawa noted that this was above the 11% prespecified threshold for futility, meaning that trial enrollment can continue.
He said there were two confirmed complete responses, six confirmed partial responses, and two yet unconfirmed partial responses, with 80% of responders having an ongoing response at the time of data cut-off.
The ORR did not appear to differ by age and was 25% among the eight patients with liver metastases.
The investigators also found that almost three quarters (74%) of patients in the study had target lesion reduction.
Tagawa reported that sacituzumab govitecan “was well tolerated, with a manageable, predictable, and consistent safety profile.”
Key treatment-related adverse events (TRAEs) of grade 3 severity or worse included neutropenia (55%), anemia (17%), febrile neutropenia (12%), and diarrhea (9%).
Three (9%) patients discontinued due to TRAEs, but there were no cases of interstitial lung disease, ocular toxicities, or grade 3 or worse neuropathy, and there were no treatment-related deaths.
Tagawa concluded that the findings “confirm prior phase I/II study results of [sacituzumab govitecan] as well-tolerated with significant antitumor activity,” in these patients.
He added that individuals with pretreated metastatic urothelial carcinoma “continue to have a high unmet medical need despite recent progress,” but “the ORR of 29% compares favorably with single-agent chemotherapy (ORR of 9%–14%).”
By Laura Cowen
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