Gilead Sciences to Withdraw Sacituzumab Govitecan Bladder Cancer Approval Status

The FDA previously granted accelerated approval to sacituzumab govitecan as a treatment for those with locally advanced or metastatic, previously treated urothelial cancer in April 2021.

Developers Gilead Sciences, Inc. have decided to voluntarily withdraw accelerated approval status for sacituzumab govitecan-hziy as a treatment for adults with locally advanced or metastatic urothelial cancer previously treated with platinum-based chemotherapy and an anti–PD-1 or anti–PD-L1 inhibitor, according to a press release from the company.¹

The developers made this decision after consulting with the FDA. The withdrawal of the urothelial cancer indication will not impact other currently improved indications for sacituzumab govitecan both in and outside of the United States. Additionally, patients in the United States who are currently receiving sacituzumab govitecan for metastatic urothelial cancer are recommended to discuss their treatment plan with their health care provider.

The FDA previously granted accelerated approval to sacituzumab govitecan as a treatment for those with locally advanced or metastatic, previously treated urothelial cancer in April 2021.² Supporting findings for the accelerated approval came from the phase 2 TROPHY-U-01 trial (NCT03547973).

Topline data showed a confirmed objective response rate (ORR) of 27.7% (95% CI, 19.6%-36.9%) among 112 evaluable patients with locally advanced or metastatic urothelial cancer, which included complete responses (CRs) in 5.4% of patients and partial responses (PRs) in 22.3%. Treatment with sacituzumab govitecan also produced a median duration of response (DOR) of 7.2 months (n = 31; 95% CI, 4.7-8.6; range, 1.4+ to 13.7).

Common toxicities among patients who received sacituzumab govitecan included neutropenia, nausea, diarrhea, fatigue, anemia, alopecia, vomiting, and constipation.

Continuation of approval status for sacituzumab govitecan in this urothelial cancer indication was dependent on findings from the phase 3 TROPiCS-04 trial (NCT04527991), which were intended to affirm the clinical benefits of the agent reported in the TROPHY-U-01 trial.

Prior findings from the TROPiCS-04 trial showed that treatment with sacituzumab govitecan did not meet the primary end point of overall survival (OS) compared with chemotherapy of physician’s choice across the intent-to-treat population.³ However, investigators observed a numerical OS improvement favoring the sacituzumab govitecan arm; there were also trends in improved outcomes across select prespecified subgroups as well secondary end points such as progression-free survival (PFS) and ORR.

Data showed that a higher proportion of patients in the sacituzumab govitecan arm died due to adverse effects compared with those who received chemotherapy. These deaths primarily occurred early in treatment and were typically associated with neutropenic complications like infection. Overall, findings from TROPiCS-04 indicated no changes to the known safety profile of sacituzumab govitecan in approved breast cancer indications or other investigational purposes.

In the open-label, international, multicenter TROPiCS-04 trial, 711 patients were assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg intravenously on day 1 and day 8 of every 21-day cycle or investigator’s choice of paclitaxel, docetaxel, or vinflunine.⁴

The trial’s primary end point was OS. Secondary end points included PFS, ORR, clinical benefit rate, DOR, safety, and quality of life.

Patients 18 years and older with histologically documented metastatic or locally advanced unresectable urothelial cancer, an ECOG performance status of 0 or 1, and progression or recurrence following platinum-containing chemotherapy and anti–PD-1 or anti–PD-L1 therapy were eligible for enrollment on the trial. Other requirements for study entry included having stable central nervous system disease for at least 4 weeks before beginning treatment, adequate hematologic counts without transfusion or growth factor support within 2 weeks of initiating treatment, and adequate hepatic function.

Those who had prior treatment with topoisomerase 1 inhibitors or an active second malignancy were ineligible for enrollment on the trial.

References

1. Gilead provides update on U.S. Indication for Trodelvy in metastatic urothelial cancer. News release. Gilead Sciences, Inc. October 18, 2024. Accessed October 28, 2024. https://tinyurl.com/2aku377j
2. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed October 28, 2024. https://bit.ly/3uTID73
3. Gilead provides update on phase 3 TROPiCS-04 study. News release. Gilead Sciences, Inc. May 30, 2024. Accessed October 28, 2024. https://tinyurl.com/yc6jevnx
4. Study of sacituzumab govitecan versus physician's choice of treatment in participants with urothelial cancer that cannot be removed or has spread (TROPiCS-04). ClinicalTrials.gov. Updated September 20, 2024. Accessed October 28, 2024. https://tinyurl.com/2mek24z7