Study Explores Sacituzumab Goveitecan Versus SOC in Metastatic or Locally Advanced Unresectable UC

The first patient with metastatic or locally advanced unresectable urothelial carcinoma (UC) has been dosed with the TROP-2-directed antibody-drug conjugate, sacituzumab goveitecan-hziy (Trodelvy) in the phase 3 TROPICS-04 clinical trial, announced Everest Medicines, in a press release.¹

Patients with metastatic or locally advanced unresectable UC have limited treatment options following progression on prior platinum-based chemotherapy and immune checkpoint inhibitor therapy. Early data from phase 2 TROPHY-U-01 (NCT03547973) exploring the use of sacituzumab goveitecan in patients with metastatic UC. The objective response rate (ORR) observed was 27% and the median overall survival (OS) was 10.5 months. Notably, these findings had a favorable comparison with single-agent chemotherapy.²

To confirm the efficacy of sacituzumab goveitecan 10 mg/kg, the drug will be compared with the physician’s choice of either paclitaxel 175 mg/m², docetaxel 75 mg/m², and vinflunine 320 mg/m² in the TROPICS-04 trial (NCT04527991).¹

"We are excited to continue advancing development of SG for people in China with metastatic UC – a devastating and fatal disease that continues to experience increasing incidence in the region," said Dr. Yang Shi, chief medical officer for Oncology at Everest Medicines, in a press release. "This comprehensive and ongoing global study has the potential to add to the existing and robust suite of data already generated for this novel therapeutic candidate."

The estimated enrollment in global, multicenter, open-label, randomized, controlled TROPICS-04 trial in 600 patients. These individuals will be assessed for the primary end point of OS, as well as the secondary end points of progression-free survival, ORR, clinical benefit rate, duration of objective tumor response, safety determined by adverse events, and quality of life.

Eligible patients for TROPICS-04 include those with histologically documented metastatic or locally advanced unresectable UC that is T4b has any number of nodes. Patients are also expected to meet the following requirements to be eligible for enrollment:

• an ECOG performance score of 0 or 1
• disease progression following platinum-based chemotherapy or anti-PD-1/PD-L1 therapy
• adequate hematologic counts without transfusion or growth factor support
• adequate hepatic function
• creatinine clearance ≥30 mL/min
• negative urine or serum pregnancy test if female
• and willingness to use contraception during the study

In terms of prior therapy and study inclusion, patients could not have received an anti-cancer monoclonal antibody within 4 weeks of receiving cycle 1 of sacituzumab goveitecan. The study also did allow patients who had received paclitaxel, docetaxel, or vinflunine, and prior treated with topoisomerase 1 inhibitors. All other prior chemotherapy was acceptable. Comorbidities such as an active second malignancy, cardiac disease active chronic inflammatory bowel disease, active serious infection, Human Immunodeficiency Virus, Hepatitis B or C, and psychiatric conditions were grounds for exclusion from the study.

Patients with metastatic or locally advanced unresectable UC are actively being recruited in 10 sites in the United States, as well as in Belgium, Canada, China, and Spain.

_References:

_{1. Everest Medicines announces first person dosed in global phase 3 registration trial of sacituzumab govitecan-hziy in China for metastatic urothelial cancer. News release. Everest Medicines. August 26, 2021. Accessed August 30, 2021. https://bit.ly/3Bn6peK}

_{2. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39(22): 2474-2485. doi: 10.1200/JCO.20.03489}

_{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. Accessed August 30, 2021. https://bit.ly/3zp2eyt}