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Sacituzumab govitecan withdrawn from bladder cancer market following negative trial
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Key Takeaways
- Sacituzumab govitecan's accelerated approval was withdrawn after failing to meet overall survival endpoints in the TROPiCS-04 trial.
- The trial showed more adverse events, particularly neutropenic complications, in the sacituzumab govitecan group compared to chemotherapy.
The decision to withdraw sacituzumab govitecan from the market was made in consultation with the US FDA following negative data from the phase 3 TROPiCS-04 trial.
Gilead has voluntarily withdrawn the US indication of sacituzumab govitecan-hziy (Trodelvy) for adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor, the company announced in a news release.1
In the TROPiCS-04 trial, sacituzumab govitecan failed to meet the trial’s primary end point of overall survival vs single-agent chemotherapy.
The FDA initially granted an accelerated approval to the Trop-2-directed antibody drug conjugate in April 2021 for this patient population.2 The approval was based on overall response rate (ORR) and duration of response data from the global phase 2 TROPHY U-01 trial (NCT03547973), which enrolled 112 patients with metastatic urothelial cancer to evaluate the safety and efficacy of sacituzumab govitecan as a monotherapy or with novel combinations.
The approval was contingent on data from confirmatory trials, including the phase 3 TROPiCS-04 trial. According to Gilead, the decision to withdraw sacituzumab govitecan from the market was made in consultation with the US FDA following negative data from this trial.
Topline results from the TROPiCS-04 trial (NCT04527991) were first reported in May 2024 in a news release from Gilead, showing that sacituzumab govitecan failed to meet the trial’s primary end point of overall survival (OS) vs single-agent chemotherapy.3
In the release, Gilead reported that a numerical improvement in OS favoring sacituzumab govitecan was observed, though the end point was not reached in the intent-to-treat population. Further, trends in improvement on the secondary end points of progression-free survival (PFS) and ORR were noted among pre-specified subgroups of patients, though the analyses were not alpha-controlled for formal statistical testing.
Among the entire study population, more deaths due to adverse events (AEs) were observed among patients who received sacituzumab govitecan vs those who received single-agent chemotherapy. AEs leading to death generally occurred early in treatment and were related to neutropenic complications, including infection.
On this, the company noted,3 “Gilead will further investigate these data, and is working to reiterate to treating physicians the importance of granulocyte-colony stimulating factor (G-CSF) use for the prevention of neutropenic complications.”
There were no new changes to the safety profile of sacituzumab govitecan for other currently approved indications.
Data from the TROPiCS-04 trial are expected to be presented at an upcoming medical meeting.
According to Gilead, there are more than 20 ongoing clinical trials assessing sacituzumab govitecan as a monotherapy and in combination with other agents in patients with solid tumors.
On the withdrawal of the therapy from the market, the company noted, “This decision does not affect the other approved Trodelvy indications within or outside of the US. Health care providers will be notified of this update. People receiving Trodelvy for metastatic urothelial cancer in the US should discuss their care with their health care provider.”1
Additional data on TROPiCS-04
The TROPiCS-04 trial was an open-label, global, multicenter, phase 3 trial that enrolled 711 patients with metastatic or locally advanced unresectable urothelial carcinoma who had received prior platinum-containing chemotherapy and checkpoint inhibitor therapy. Patients were randomly assigned 1:1 to receive sacituzumab govitecan or single-agent chemotherapy of the physician’s choice (consisting of the standard of care options of paclitaxel, docetaxel, or vinflunine).
Sacituzumab govitecan was administered intravenously at the dose level of 10 mg/kg on day 1 and day 8 of 21-day cycles.4 Chemotherapy with paclitaxel, docetaxel, or vinflunine was administered at the dose levels of 175, 75, and 320 mg/m2, respectively, every 3 weeks on day 1 of 21-day cycles.
The primary end point for the trial was OS. Secondary end points included PFS, ORR, clinical benefit rate, and duration of objective tumor response per RECIST v1.1 and blinded independent central review.
References
1. Gilead provides update on U.S. indication for Trodelvy in metastatic urothelial cancer. News release. Gilead. October 18, 2024. Accessed October 21, 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. News release. US Food & Drug Administration. April 13, 2021. Accessed May 31, 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 Sciences. May 30, 2024. Accessed October 21, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/5/gilead-provides-update-on-phase-3-tropics-04-study
4. Study of sacituzumab govitecan-hziy (IMMU-132) versus treatment of physician's choice in participants with metastatic or locally advanced unresectable urothelial cancer (TROPiCS-04). ClinicalTrials.gov. Last updated May 6, 2024. Accessed October 21, 2024. https://www.clinicaltrials.gov/study/NCT04527991
