FDA Grants Sacituzumab Govitecan Fast Track Designation for Urothelial Carcinoma

The FDA has granted a fast track designation to sacituzumab govitecan for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma.

The FDA has granted a fast track designation to the antibody-drug conjugate (ADC) sacituzumab govitecan for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor, and a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, including patients who are platinum ineligible and have previously received a PD-1/PD-L1 inhibitor in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.1

In findings of a cohort from the single-arm phase II TROPHY-U-O1 trial presented at the 2019 ESMO Congress, sacituzumab govitecan demonstrated clinical activity with an overall response rate (ORR) of 29% in patients with heavily pretreated metastatic urothelial carcinoma.2

“Coming in the wake of a recent unanimous recommendation by the independent Data Safety Monitoring Committee for the ASCENT study to stop the trial due to compelling evidence of efficacy in metastatic triple-negative breast cancer, it is gratifying to learn of the FDA’s recognition of sacituzumab govitecan’s potential in urothelial cancer, an important second indication for our lead antibody-drug conjugate. With the upcoming maturation of the data from the 100-patient cohort with prior platinum-based and PD-1 or PD-L1 inhibitor therapies, and based on the Fast Track designation, we will actively seek guidance from the FDA on a potential accelerated approval pathway,” Loretta M. Itri, MD, chief medical officer at Immunomedics, the manufacturer of sacituzumab govitecan, said in a press release.

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.

Prior to the TROPHY-U-01 trial, the phase I/II single-arm basket study IMMU-132-01 evaluated sacituzumab govitecan 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).3 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%. The 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, preliminary data were presented 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.

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; 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.

In its press release, Immunomedics provided an update on TROPHY-U-O1, reporting that the full 100-patient cohort 1 has been enrolled, with results anticipated later this year. Enrollment in cohort 2 will likely be completed later this year, and the company has added an additional cohort that will evaluate sacituzumab govitecan plus pembrolizumab in patients who have not previously received a PD-1/PD-L1 inhibitor.

Immunomedics recently reported that the confirmatory phase III ASCENT study exploring sacituzumab govitecan in patients with metastatic triple-negative breast cancer (TNBC) has been stopped due to “compelling evidence of efficacy.”4

The company halted the trial based on a unanimous recommendation from the independent Data Safety Monitoring Committee. The ASCENT trial was launched to confirm the positive efficacy and safety results reported in a phase II study of the ADC in TNBC.

In December 2019, the FDA accepted a biologics license application (BLA) seeking an accelerated approval for sacituzumab govitecan as a treatment for patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease.5 The FDA is scheduled to decide on the BLA by June 2, 2020. An accelerated approval, which would be based on the submitted phase II data, would be contingent upon confirmatory findings, which Immunomedics will now be able to provide with the positive ASCENT results.


  1. FDA Grants Fast Track Designation To Sacituzumab Govitecan For Locally-Advanced Or Metastatic Urothelial Cancer. Published April 7, 2020. https://yhoo.it/3c0jUnS. Access April 7, 2020.
  2. 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.
  3. 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.
  4. Immunomedics Announces ASCENT Study to be Stopped for Compelling Efficacy Published April 6, 2020. https://bit.ly/2RgJ3mu. Accessed April 6, 2020.
  5. Immunomedics Announces FDA Acceptance for Filing of Biologics License Application Resubmission for Sacituzumab Govitecan to Treat Metastatic Triple-Negative Breast Cancer. Immunomedics, Inc. Published December 26, 2019. https://bit.ly/37iQ4ZD. Accessed December 27, 2019.

The ORR comprised 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%.