Results from an interim Phase II study with sacituzumab govitecan (IMMU-132) shows that the investigational agent is active in patients with metastatic urothelial cancer (mUC) who have relapsed or are refractory to chemotherapies and immune checkpoint inhibitors or IOs.
Metastatic or unresectable disease is identified in approximately 20% of patients presenting with invasive urothelial cancer.  This makes the disease the sixth most common cancer in the United States after lung cancer, prostate cancer, breast cancer, colon cancer, and lymphoma. According to the American Cancer Society, the estimated number of new cases in 2017 is 79.030 and deaths from bladder cancer will reach 16,870. 
The results [sacituzumab govitecan] in patients relapsed or refractory to both chemotherapy and therapy with immune checkpoint inhibitors are particularly encouraging, since few options are available for these patients after they become refractory…
“The results in patients relapsed or refractory to both chemotherapy and IO therapies are particularly encouraging, since few options are available after they become refractory,” noted Scott T. Tagawa, the Richard A. Stratton Associate Professor in Hematology and Oncology, and an Associate Professor of Clinical Medicine and of Clinical Urology at Weill Cornell Medicine, who presented the results at the ESMO 2017 Congress held September 8 – 12, 2017 in Madrid, Spain.
Despite the fact that five IOs have been approved in the U.S. for patients with advanced bladder cancer following platinum chemotherapy, only about 15% to 25% of patients respond to the new treatments. I believe sacituzumab govitecan has the potential to become a second or later line treatment to platinum- or IO-based therapy,” Tagawa added. 
In the single-arm Phase II study with sacituzumab govitecan, the confirmed Objective Response Rate (ORR) among forty-one intention-to-treat patients was 34% (14/41), including two confirmed Complete Responses (CRs) and twelve confirmed Partial Responses (PRs). While eight of the fourteen responders are ongoing and are still receiving treatment, including four long-term responses greater than 1 year and two currently ongoing at 15 and 22 months, the median Duration of Response (DOR) at the time of data cutoff was 12.6 months (95% confidence interval [CI], 7.5 to 12.9 months).
Median PFS at 80% data maturity was 7.1 months (95% CI, 5.0 to 10.7 months).
The enrolled cohort included fourteen patients who progressed after prior IO therapy, eleven of whom received IMMU-132 as the fourth or later line of therapies.
Despite the late-stage setting, the confirmed ORR in this subset of patients was 29% (4/14), with median PFS of 5.4 months (95% CI, 1.9 to 7.2 months) but median OS was not met.
All four responders in this subgroup had three or more prior therapies before being treated with sacituzumab govitecan.
“In light of these favorable interim results with sacituzumab govitecan in metastatic urothelial cancer, we will approach the regulatory authorities to discuss the appropriate path forward in this disease with continued unmet medical need,” concluded Behzad Aghazadeh, Chairman of the Board of Immunomedics.
A total of 41 patients with mUC were enrolled into this open-label multicenter study to receive 10 mg/kg of sacituzumab govitecan on days 1 and 8 of 3-week cycles. Median number of doses received was 3 (range, 1-6). Despite repeated dosing, grade 3 or higher adverse events were limited to neutropenia (39%), anemia (10%), diarrhea (7%), and fatigue (7%).
Tagawa has served as a consultant to and receives research funding from Immunomedics.