The Food and Drug Administration (FDA) has granted accelerated approval to Trodelvy® (sacituzumab govitecan-hziy) for the treatment of locally advanced or metastatic urothelial cancer in patients previously treated with a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.

Sacituzumab govitecan, a Trop-2-directed antibody and topoisomerase inhibitor conjugate, binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38, the active metabolite of irinotecan. The resulting DNA damage leads to apoptosis and cell death.

The accelerated approval was based on data from the multicenter, open-label, phase 2 TROPHY study ( NCT03547973), which assessed the efficacy and safety of sacituzumab govitecan in 112 patients with locally advanced or metastatic urothelial cancer after failure of a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.

Patients received sacituzumab govitecan intravenously once weekly on days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR); a key secondary endpoint included duration of response (DOR).

Results showed an ORR of 27.7% (95% CI, 19.6-36.9), with 5.4% of patients achieving a complete response and 22.3% having a partial response. Among responders, the median DOR was 7.2 months (n=31; [95% CI, 4.7-8.6]; range, 1.4+, 13.7).

As for safety, the most common adverse reactions (incidence of greater than or equal to 25%) included neutropenia, nausea, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, decreased appetite, rash, and abdominal pain.

“Only a fraction of patients derives long-term benefit from previously approved cytotoxic therapy or immunotherapy, leaving a great unmet need for treatment options for patients with advanced urothelial cancer who have progressed on first- and second-line therapies,” said Scott T. Tagawa, MD, MS, FACP, Professor of Medicine and Urology at Weill Cornell Medicine, an oncologist at New York-Presbyterian/Weill Cornell Medical Center and principal investigator of the TROPHY study. “The response rate and tolerability seen with sacituzumab govitecan-hziy may provide physicians an effective new treatment option for patients whose cancer continues to progress even after multiple therapies.”

Trodelvy is supplied as 180mg lyophilized powder in single-dose vials. The product is not a substitute and should not be used with other drugs containing irinotecan or its active metabolite SN-38.


FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; April 13, 2021.