Barcelona, Spain ( Human trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein which is highly expressed in urothelial carcinoma cells, thereby constituting a promising target for antibody-drug conjugate therapy.1 Sacituzumab govitecan is an antibody-drug conjugate comprised of the Trop-2 humanized monoclonal antibody sacituzumab coupled to SN-38, the active metabolite of irinotecan via a hydrolysable biochemical linker. Sacituzumab govitecan is a relatively unique antibody-drug conjugate in that it exhibits a high drug:antibody ratio and the linker is able to undergo hydrolysis both intracellularly and extracellularly, thereby targeting both Trop-2-expressing urothelial cancer cells as well as the tumor microenvironment so as to create a “bystander effect.”2,3 Sacituzumab govitecan has already demonstrated efficacy in a number of different solid tumors and a  is currently in phase III development for triple-negative breast cancer.4


Scott Tagawa, MD, MS, previously presented data on 45 patients in the urothelial carcinoma cohort of a phase I/II basket study of sacituzumab govitecan across multiple epithelial cancers.5 Based on a promising 31% objective response rate among this cohort of heavily pre-treated advanced urothelial carcinoma patients, investigators sought to conduct TROPHY-U-01, a multicohort open-label phase II trial of sacituzumab govitecan (10 mg/kg on days 1 and 8 of a 28-day cycle) in patients with treatment-refractory metastatic urothelial cancer. Today, Dr. Tagawa presents an interim data analysis from 35 of 100 planned patients on cohort 1, which is comprised of patients who had progressed despite prior platinum-based chemotherapy and checkpoint blockade immunotherapy. Patients were treated until disease progression or unacceptable toxicity, and the primary endpoint was objective response rate.


At baseline, the 35 evaluable patients had a median age of 64, were 80% male, and had received a median 3 prior lines of systemic therapy. Additionally, 63% (22/35) of patients had visceral metastases, including 23% (8/25) with liver metastases.


In general, treatment was well-tolerated. The most common grade ≥3 adverse events were leukopenia, anemia, febrile neutropenia, and infection. Of note only 9 of these 35 patients received prophylactic growth factor support. Diarrhea occurred in the majority of patients but was generally mild. No treatment-related deaths occurred. 


At a median follow-up of 4.1 months, 57% of patients remained on treatment, and the objective response rate was 29% (10/35), including 6% (2/35) that had a complete response.


Of the 10 patients who achieved an objective response, 8 responses were ongoing at the time of last data cut-off.

Only two patients had progression of disease as their best response, and 74% (26/35) of patients achieved at least some tumor shrinkage.

While follow-up is not yet mature, it appears that in general responses and disease stability were maintained during treatment.

In summary, this interim analysis from TROPHY-U-01 demonstrated that sacituzumab govitecan is generally well-tolerated with a manageable toxicity profile. The observed 29% objective response rate in the third-line setting or later is particularly encouraging in the context of known low response rates to cytotoxic chemotherapy and immunotherapy in platinum-refractory metastatic urothelial carcinoma. Ongoing follow-up data from TROPHY-U-1 are eagerly anticipated. Future work will aim to better characterize the toxicity profile from this agent which will be especially important in optimizing the managmenet of treatment-related neurtropenia. Combination therapy, especially with immune chekpoint blockade may be a promising approach in future studies. 

Presented by: Scott T. Tagawa, MD, The Richard A. Stratton Associate Professor in Hematology and Oncology, Weill Cornell Medical College, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York

Written by: Michael Lattanzi, MD, Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center, Twitter: @MikeLattanzi, at the 2019 European Society for Medical Oncology Congress (#ESMO19), September 27 – October 1, 2019, Barcelona, Spain


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