Sacituzumab Govitecan Demonstrates Early Efficacy in Heavily Pretreated Metastatic Urothelial Cancer

The antibody–drug conjugate sacituzumab govitecan induced objective responses in about 30% of heavily pretreated patients with metastatic urothelial carcinoma in initial results of a phase II trial that were presented at the 2019 ESMO Congress.

Scott T. Tagawa, MD

The antibody—drug conjugate sacituzumab govitecan induced objective responses in about 30% of heavily pretreated patients with metastatic urothelial carcinoma in initial results of a phase II trial that were presented at the 2019 ESMO Congress.1

In the single-arm TROPHY-U-O1 trial, the overall response rate (ORR) of 29% consisted of 2 complete responses, 6 partial responses (PRs), and 2 additional PRs pending confirmation. In patients with liver metastases (n = 23), the ORR was 25.0%, lead study author Scott T. Tagawa, MD, stated in a presentation during the meeting. Sacituzumab govitecan was also found to be well tolerated with a manageable and predictable safety profile.

“The TROPHY-U-01 study confirms the previously presented clinical activity of sacituzumab govitecan in heavily pretreated patients with advanced urothelial carcinoma. Sacituzumab govitecan was overall well tolerated with a safety profile consistent with prior reports, with the most common toxicity of myelosuppression, which is reasonably managed with growth factors and/or dose reductions,” said Tagawa, Richard A. Stratton Associate Professor in Hematology and Oncology, associate professor of clinical medicine & urology at Weill Cornell Medicine, associate attending physician, NewYork-Presbyterian—Weill Cornell Medical Center. “These data, combined with the prior available data, demonstrate that sacituzumab govitecan has the potential to change the landscape of advanced urothelial carcinoma.”

Patients with metastatic urothelial carcinoma who progress on platinum-based therapy have limited therapeutic options and poor outcomes, with ORRs at approximately 10%. Checkpoint inhibitors have also not been effective in the majority of these patients, emphasizing the need for additional treatments.

Sacituzumab govitecan, a Trop-2—directed antibody–drug conjugate, has also shown significant clinical activity in other solid tumors, such as metastatic triple-negative breast cancer. Trop-2 is an epithelial cell surface antigen that is highly expressed in urothelial cancer.

In the phase I/II single-arm basket study IMMU-132-01, sacituzumab govitecan was evaluated in patients with advanced epithelial cancers, including a metastatic urothelial cancer cohort in which the median number of prior therapies was 2 (range, 1-6). In the overall cohort (n = 45), the ORR was 31% and, in patients who received prior platinum-based therapy and checkpoint inhibitors (n = 15), the ORR was 27%.2The median progression-free survival (PFS) was 7.3 months (95% CI, 5.0-10.7) and the median overall survival (OS) was 16.3 months (95% CI, 9.0-31.0). The data warranted further investigation and the rationale to develop a phase II trial.

In the open-label, phase II TROPHY-U-01 trial, investigators evaluated sacituzumab govitecan in 2 cohorts: patients with metastatic urothelial cancer who progressed after platinum-based therapy and checkpoint inhibition (n = 100; cohort 1), and those who were ineligible for platinum-based therapy and progressed following prior checkpoint inhibitor treatment (n = 40; cohort 2).

At the 2019 ESMO Congress, Tagawa presented preliminary data from cohort 1, which was a Simon 2-stage design with 90% power to reject the null hypothesis of ≤12% ORR. The preplanned interim analysis was based on an investigator assessment of data as per RECIST v1.1 criteria of cohort 1. Furthermore, the first stage included a prespecified futility stopping rule if ≤4 responses were observed out of 35 patients.

Patients received sacituzumab govitecan at 10 mg/kg on days 1 and 8 every 3 weeks, and treatment was continued until unacceptable toxicity or disease progression. The primary endpoint was ORR; secondary endpoints were safety/tolerability, duration of response, PFS, and OS. The 35 patients included in the interim analysis received ≥1 cycle of sacituzumab govitecan and had ≥1 on-treatment response assessment.

The median age was 64 years (range, 43-90), with 20% of patients ≥75 years. Most patients were male (80%) and white (83%), and more than half had an ECOG performance status of 1 (57%). Of those with visceral metastases, most were in the lung (40%), followed by liver (23%), and other (11%). The median number of prior therapies was 3 (range, 2-6), and the median duration of the last anticancer regimen was 1.6 months (range, 1-60).

At a median follow-up of 4.1 months, results showed that 74% of patients experienced a reduction in tumor size. The median time to onset response was 1.5 months (range, 1.2-2.8). Although preliminary, responses were higher in patients <75 years (n = 8), in those with ≥3 prior anticancer regimens (n = 8), and in patients with 0 to 1 Bellmunt risk factors (n = 10). As of the data cutoff, 8 of the 10 responders have an ongoing response.

“While admittedly each of these subgroups is small, it appears that the response rate is consistent across subgroups,” Tagawa said.

Regarding safety, all-grade treatment-related adverse events (TRAEs) included alopecia (74%), neutropenia (66%), diarrhea (57%), and fatigue (54%). Grade 3/4 TRAEs included neutropenia (55%), leukopenia (29%), anemia (17%), febrile neutropenia (12%), decrease in lymphocyte count (9%), diarrhea (9%), urinary tract infection (11%), fatigue (6%), and abdominal pain (3%). Most cases of diarrhea were grade 1/2, Tagawa said, adding that grade ≥2 rash occurred in 5 patients. There were no cases of grade >2 peripheral neuropathy or interstitial lung disease reported. Three patients discontinued treatment due to TRAEs, and no treatment-related deaths occurred.

Ignacio Duran Martinez, MD, PhD, of the Department of Medical Oncology Hospital University Virgen del Rocío Instituto de Biomedicina de Sevilla, Seville, Spain, explained in a presentation that these data are encouraging, but are also very preliminary.

“It is too early, it probably will be [clinically meaningful], but it is too early. We need to complete randomized controlled trials. We [are also] waiting to see whether combinations are going to be superior.”

As the interim results from cohort 1 of the TROPHY-U-01 surpassed the prespecified futility endpoint, the cohort continues to enroll. Cohort 2 of the trial is also enrolling.


  1. Tagawa STT, Balar A, Petrylak DP, et al. Initial results from TROPHY-U-01: a phase 2 open-label study of sacituzumab govitecan in patients with metastatic urothelial cancer (mUC) after failure of platinum-based regimens or immunotherapy. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019; Barcelona, Spain. Abstract LBA55.
  2. Tagawa S, Faltas BM, Lam ET, et al. Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): results from a phase I/II study.J Clin Oncol. 2019;37(suppl 7S; abstr 354). doi: 10.1200/JCO.2019.37.7_suppl.354.