Gilead to Withdraw U.S. Approval for Trodelvy in Metastatic Urothelial Cancer After TROPiCS-04 Failure
Key Insights
Gilead Sciences will voluntarily withdraw the U.S. accelerated approval for Trodelvy in metastatic urothelial cancer (search) following consultation with the FDA.
The decision is based on the TROPiCS-04 study failing to meet its primary endpoint of overall survival in the intention-to-treat population.
This withdrawal does not affect other approved Trodelvy indications, including those for metastatic TNBC (search) and HR+/HER2- metastatic breast cancer (search).
Gilead Sciences has announced its plan to voluntarily withdraw the U.S. accelerated approval for Trodelvy (sacituzumab govitecan-hziy) in adult patients with locally advanced or metastatic urothelial cancer (search) who have previously received platinum-based chemotherapy and either a PD-1 (search) or PD-L1 (search) inhibitor. This decision, made in consultation with the FDA, follows the failure of the confirmatory TROPiCS-04 study to demonstrate a statistically significant improvement in overall survival (OS). The withdrawal is specific to the urothelial cancer indication and does not impact other approved uses of Trodelvy.
Background on Trodelvy in Urothelial Cancer
Trodelvy received accelerated approval in 2021 for metastatic urothelial cancer (search) based on promising tumor response rate and duration of response data from the Phase 2 TROPHY-U-01 study. This approval was contingent upon verification of clinical benefit in the confirmatory TROPiCS-04 trial.
TROPiCS-04 Trial Results
The TROPiCS-04 study, designed to confirm the benefits observed in earlier trials, failed to meet its primary endpoint of overall survival (OS) in the intention-to-treat (ITT) population. Detailed data from the TROPiCS-04 trial will be presented at an upcoming medical meeting. The specific reasons for the trial's failure were not disclosed in the announcement, but the lack of improved OS was the key factor in Gilead's decision to withdraw the accelerated approval.
Impact on Patients and Clinical Practice
Gilead is notifying healthcare providers about this change, advising them to discuss alternative treatment options with patients currently receiving Trodelvy for metastatic urothelial cancer (search) in the U.S. The company emphasized that this decision does not affect other approved Trodelvy indications. Trodelvy remains approved for use in unresectable locally advanced or metastatic triple-negative breast cancer (TNBC (search)) after two or more prior systemic therapies, and for HR+/HER2- metastatic breast cancer (search) after endocrine-based therapy and at least two additional systemic therapies.
Ongoing Research and Future Directions
Trodelvy, a first-in-class Trop-2 (search)-directed antibody-drug conjugate (ADC), continues to be evaluated in over 20 ongoing clinical trials as a monotherapy and in combination with other agents across various solid tumors, including lung and gynecological cancers. These trials aim to expand the utility of Trodelvy in areas of unmet medical need. The drug's mechanism of action, involving a proprietary hydrolyzable linker attached to SN-38 (a topoisomerase I inhibitor), allows it to target Trop-2 expressing cells and the tumor microenvironment, potentially offering a bystander effect.