Dr Park on the Rationale for the TROPHY-U-01 Trial in Urothelial Carcinoma

Chandler H. Park, MD, FACP, medical oncologist, Norton Healthcare, discusses the rationale for evaluating sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) in cohort 3 of the phase 2 TROPHY-U-01 trial (NCT03547973) in patients with metastatic urothelial carcinoma who have progressed following platinum-based chemotherapy.

Bladder cancer presents a formidable treatment challenge due to its high levels of aggressiveness, particularly evident in stage IV cases where the 5-year overall survival rate is known to be less than 5%, Park begins. Although treatments such as pembrolizumab and platinum-based therapies are available for patients in this population, the efficacy of these regimens often falls short of what is desired, Park states. The TROPHY-U-01 trial focused on patients with stage IV metastatic urothelial cancer whose condition worsened after initial platinum-based chemotherapy, including those who experienced progression within 12 months of neoadjuvant chemotherapy, he explains. Notably, approximately 40% of patients had not responded to neoadjuvant chemotherapy within this time frame, Park adds.

Typically, patients receive immunotherapy following platinum-based chemotherapy in the metastatic setting, either pembrolizumab or the maintenance therapy approach from the phase 3 JAVELIN Bladder 100 (NCT02603432) study, which was avelumab (Bavencio), he continues. The TROPHY-U-01 study investigated whether combining sacituzumab govitecan, an antibody-drug conjugate, with pembrolizumab could enhance overall response rate (ORR) and duration of response (DOR), thereby improving clinical benefit rates (CBRs), Park elucidates. Patients, who were naive to checkpoint inhibitors, had experienced metastatic bladder cancer progression following platinum-based chemotherapy in the metastatic setting or within 12 months in the neoadjuvant setting, he notes.

The treatment of patients enrolled in the phase 3 study involved administering 10 mg/kg of sacituzumab govitecan on days 1 and 8, along with pembrolizumab on day 1 of each 21-day cycle, Park expands. The primary end point of the trial was ORR, and secondary end points included CBR, DOR, and progression-free survival as assessed by central review, he concludes.