FDA Approves Sacituzumab Govitecan for Advanced Urothelial Cancer

FDA

The FDA has granted an accelerated approval to sacituzumab govitecan (Trodelvy) 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.¹

The regulatory decision was based on data from the TROPHY-U-01 trial (IMMU-132-06; NCT03547973), which showed that the agent elicited a confirmed objective response rate (ORR) of 27.7% (95% CI, 19.6-36.9, which included a 5.4% complete response rate and a 22.3% partial response rate. The median duration of response (DOR) achieved with sacituzumab govitecan was 7.2 months (95% CI, 4.7-8.6; range 1.4+, 13.7).

The trial evaluated the agent in the following 3 cohorts: those with metastatic urothelial carcinoma who progressed on previous platinum-based and checkpoint inhibitors (cohort 1; n = 100), those with metastatic urothelial carcinoma who were not eligible for platinum-based therapy and who had progressed following previous checkpoint inhibitors (cohort 2; n = 40), and patients with metastatic urothelial carcinoma who were naïve to checkpoint inhibitors and who had progressed on previous platinum-based treatment (cohort 3; n = up to 61 patients).²

Participants were given 10 mg/kg of sacituzumab govitecan on days 1 and 8 every 21 days. Treatment was given until loss of clinical benefit or intolerable toxicity. The primary objective of the trial was ORR by central review, while secondary objectives comprised safety/tolerability, DOR, progression-free survival (PFS), and overall survival (OS).

Among the 113 patients in cohort 1, the median age was 66 years (range, 33-90). with 23% of patients aged 75 years or older. The majority of patients were White (74%) and had an ECOG performance status of 1 (72%). Twenty-eight percent of patients had visceral metastasis in the liver and the median number of prior regimens received was 3.0 (range, 1-8).

In cohort 1, the median PFS with sacituzumab govitecan was 5.4 months (95% CI, 3.5-6.9), while the median OS was 10.5 months (95% CI, 8.2-12.3).

The most frequently reported adverse effects (AEs) that occurred in over 25% of patients who received sacituzumab govitecan included neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain.

In cohort 1 specifically, 6% of patients (n = 7) discontinued treatment because of treatment-related AEs; 3 of these patients discontinued because of neutropenia or its complications. Thirty percent of patients required management with granulocyte colony–stimulating factor. One treatment-related death was reported; this patient experienced sepsis in result of febrile neutropenia.

The indication is approved under accelerated approval based on tumor response rate and DOR. Continued approval will be contingent upon verification of clinical benefit in the confirmatory phase 3 TROPiCS-04 trial (NCT04527991).

References

1. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed April 13, 2021. https://bit.ly/3tgxmgy
2. Loriot Y, Balar AV, Petrylak DP, et al. TROPHY-U-01 cohort 1 final results: a phase II study of sacituzumab govitecan (SG) in metastatic urothelial cancer (mUC) that has progressed after platinum (PLT) and checkpoint inhibitors (CPI). Ann Oncol. 2020;31(suppl 4):S1156. doi:10.1016/j.annonc.2020.08.2253