FDA Grants Accelerated Approval to Sacituzumab Govitecan for Metastatic Urothelial Cancer

Based on results of the phase 2 TROPHY-U-01 trial, the FDA has given accelerated approval to sacituzumab govitecan for previously treated, locally advanced or metastatic urothelial carcinoma.

The FDA granted accelerated approval to sacituzumab govitecan (Trodelvy) to treat patients with locally advanced or metastatic urothelial carcinoma after having received either a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.1

The action by the agency was based on findings from the phase 2 TROPHY-U-01 trial (NCT03547973) of the Trop-2–directed antibody-drug conjugate in the indicated patient population. Updated response data indicate an objective response rate (ORR) of 27.7% (95% CI, 19.6%-36.9%), comprised of 5.4% complete responses and 22.3% partial responses. A median duration of response (DOR) of 7.2 months (95% CI, 4.7-8.6) in 31 patients was noted.

“The final results from TROPHY-U-01 cohort 1 confirmed the interim findings and the results from the prior phase 1 study, and showed that sacituzumab govitecan is generally well tolerated and has significant anticancer activity in heavily pretreated [patients with] metastatic urothelial cancer who have progressed on both platinum-based chemotherapy and checkpoint inhibitors,” Yohann Loriot, MD, PhD, lead author of the study and a medical oncologist at the Institut de Cancèrologie Gustave Roussy, in Villejuif, France, said in a presentation during the meeting.

The single-arm, multicenter trial enrolled 112 patients with locally advanced disease who had been previously treated with platinum-based chemotherapy and a PD-1/PD-L1–directed immune checkpoint inhibitor. Sacituzumab govitecan was given intravenously at 10 mg/kg on days 1 and 8 of each 3-week cycle. The primary end point was ORR with secondary outcomes including DOR, progression-free survival (PFS), and overall survival (OS).

Results from the study were previously presented at the European Society for Medical Oncology 2020 Congress (ESMO 2020).2 At that time, the estimated median PFS with sacituzumab govitecan was 5.4 months (95% CI, 3.5-6.9), while the estimated median OS was 10.5 months (95% CI, 8.2-12.3).

The median number of prior anticancer regimens in the patient population was 3. “Therefore, this is a heavily pretreated patient population, and sacituzumab govitecan was the fourth line of therapy,” noted Loriot.

Sacituzumab govitecan is generally considered safe, with diarrhea as the most commonly experienced treatment-related adverse effect (AE) reported at ESMO 2020 occurring in more than two-thirds of patients (all grade, 65%). This is consistent with what has been reported in prior studies with the agent in other tumor types. Nine percent of patients experienced grade 3 diarrhea and only 1% experienced it as grade 4. Other notable AEs included neutropenia, nausea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain.

Additionally, a phase 3 trial confirmatory trial TROPiCs-04 (NCT04527991) is set to enroll 482 patients with locally advanced and resectable or metastatic urothelial carcinoma who have progressed following platinum-based chemotherapy and checkpoint inhibition. Patients will be randomized 1:1 to either intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 3-week cycle or physician’s choice of paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2.

Prior to the approval, sacituzumab govitecan was granted fast track designation for this indication in April 2020.3 Earlier this month, accelerated approval for the agent in triple-negative breast cancer after 2 or more prior systemic therapies, with at least 1 therapy for metastatic disease, was converted to a full approval based on phase 3 data.


1. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed April 13, 2021. https://bit.ly/3uTID73

2. Loriot Y, Balar AV, Petrylak DP, et al. Final results from TROPHY-U-01 cohort 1: a phase 2 open-label study of sacituzumab govitecan (SG) in patients with metastatic urothelial cancer (mUC) and disease progression after platinum (PLT)-based reigmens and checkpoint inhibitors. Ann Oncol. 2020;31(suppl 4):S1142-S1215. doi: 10.1016/annonc/annonc325.

3. FDA Grants Fast Track Designation To Sacituzumab Govitecan For Locally-Advanced Or Metastatic Urothelial Cancer. News release. Immunomedics, Inc. April 7, 2020. Accessed April 13, 2021. https://yhoo.it/3c0jUnS