Sacituzumab govitecan falls short in phase 3 trial for metastatic urothelial carcinoma

Topline results from the phase 3 TROPiCS-04 trial (NCT04527991) showed that sacituzumab govitecan-hziy (Trodelvy) failed to meet the primary end point of overall survival (OS) vs single-agent chemotherapy in patients with metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and anti-PD-(L)1 therapy, Gilead Sciences announced in a news release.¹

There are no new changes to the known safety profile of sacituzumab govitecan for the approved indications.

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 overall response rate (ORR) were noted among pre-specified subgroups of patients, though the analyses were not alpha-controlled for formal statistical testing. These data are expected to be presented at an upcoming medical meeting.

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,¹ “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 are no new changes to the known safety profile of sacituzumab govitecan for the approved indications.

Gilead also noted that they are discussing the findings and next steps with the FDA. In April 2021, the FDA granted an accelerated approval indication to sacituzumab govitecan for patients with locally advanced or metastatic urothelial carcinoma who have previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.² The approval was based on ORR and duration of response data from the phase 2 TROPHY U-01 trial (NCT03547973), which enrolled 112 patients to evaluate the safety and efficacy of sacituzumab govitecan as a monotherapy or with novel combinations.

Continued approval of sacituzumab govitecan for this indication is contingent upon data from confirmatory trials, including the TROPiCS-04 trial.

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.³ 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 phase 3 TROPiCS-04 Study. News release. Gilead Sciences. May 30, 2024. Accessed May 31, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/5/gilead-provides-update-on-phase-3-tropics-04-study

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. 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 May 31, 2024. https://www.clinicaltrials.gov/study/NCT04527991