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.

References

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