Gilead to Withdraw US Indication for Sacituzumab Govitecan in Metastatic Urothelial Cancer

The United States (US) indication for sacituzumab govitecan-hziy (Trodelvy) in the treatment of adult patients with pretreated, locally advanced or metastatic urothelial cancer will be voluntarily withdrawn by Gilead, according to an announcement from the company.¹

The decision was made in conjunction with the FDA. In April 2021, the regulatory agency granted accelerated approval to the antibody-drug conjugate (ADC) for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.²

The accelerated approval was supported by data from the phase 2 TROPHY-U-01 trial (NCT03547973), and the phase 3 TROPiCS-04 trial (NCT04527991) was serving as the confirmatory study to support full approval.

However, in May 2024, Gilead announced that TROPiCS-04 did not meet its primary end point of overall survival (OS) when comparing sacituzumab govitecan vs physician’s choice of single-agent chemotherapy in patients with locally advanced or metastatic urothelial cancer who received prior treatment with platinum-containing chemotherapy and anti–PD-1/PD-L1 therapy.³

A numerical improvement in OS was observed with sacituzumab govitecan in the intention-to-treat population; trends favoring the ADC were seen in prespecified subgroups for secondary end points of progression-free survival (PFS) and overall response rate (ORR).

In the announcement, Gilead noted that the decision to withdraw the indication for sacituzumab govitecan in advanced urothelial cancer will not affect any other indications for the agent in the US or internationally.¹

“Health care providers will be notified of this update. People receiving [sacituzumab govitecan] for metastatic urothelial cancer in the US should discuss their care with their health care provider,” the company wrote in the news release.

Full data from TROPiCS-04 will be presented at an upcoming medical conference.

TROPiCS-04 Overview

The randomized, open-label study enrolled patients at least 18 years of age with histologically documented metastatic or locally advanced, unresectable urothelial cancer.4 Patients needed to have T4b, any N or any T, N 2-3 tumors of upper and lower urinary tract, and those with mixed histologic types were allowed if urothelial was the predominant histology. Disease progression or recurrence was required following a platinum-containing regimen and anti–PD-1/PD-L1 therapy in the locally advanced or metastatic setting.

Other key inclusion criteria consisted of an ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. Patients with previously treated brain metastases were allowed to participate if they had stable central nervous system disease for at least 4 weeks prior to the first study treatment.

Key exclusion criteria included prior treatment with a monoclonal antibody or ADC within 4 weeks of the first day of treatment; prior chemotherapy, targeted therapy, or radiation within 2 weeks of the first day of cycle 1; prior treatment with any of the standard-of-care chemotherapies for urothelial cancer used in the control arm; any prior treatment with topoisomerase 1 inhibitors; and active cardiac disease.

Enrolled patients were randomly assigned to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle; or physician’s choice of chemotherapy consisting of paclitaxel at 175 mg/m2, docetaxel at 75 mg/m2, or vinflunine at 320 mg/m2 on day 1 of each 21-day cycle.

Other secondary end points included clinical benefit rate, duration of response, safety, and quality of life.

Safety data from TROPiCS-04 showed that there was a higher rate of adverse effects leading to death in the sacituzumab govitecan arm, which primarily occurred early in treatment and were related to neutropenic AEs, including infection.³

References

1. Gilead provides update on U.S. indication for Trodelvy in metastatic urothelial cancer. News release. October 18, 2024. Accessed October 18, 2024. https://www.gilead.com/company/company-statements/2024/gilead-provides-update-on-us-indication-for-trodelvy-in-metastatic-urothelial-cancer
2. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed October 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer
3. Gilead provides update on phase 3 TROPiCS-04 study. News release. Gilead. May 30, 2024. Accessed October 18, 2024. https://www.gilead.com/news/news-details/2024/gilead-provides-update-on-phase-3-tropics-04-study
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 18, 2024. https://clinicaltrials.gov/study/NCT04527991