Sacituzumab Govitecan Yields Consistent Benefit in Platinum-Ineligible mUC

Data from the phase 2 TROPHY-U-01 trial support further evaluation of sacituzumab govitecan in patients with metastatic urothelial cancer following immune checkpoint inhibitor therapy, according to the lead investigator.

Sacituzumab govitecan-hziy (Trodelvy) produced consistent benefits in terms of objective response rate (ORR) among patients with platinum-ineligible metastatic urothelial cancer (mUC) after disease progression on immune checkpoint inhibitors (CPI), according to data from cohort 2 of the phase 2 TROPHY-U-01 trial (NCT03547973) presented at the 2023 Genitourinary Cancers Symposium.1

In cohort 2 of TROPHY-U-01, sacituzumab govitecan "had a manageable safety profile with no new safety signals and no treatment-related deaths," according to an expert from Yale School of Medicine.

In cohort 2 of TROPHY-U-01, sacituzumab govitecan "had a manageable safety profile with no new safety signals and no treatment-related deaths," according to an expert from Yale School of Medicine.

In cohort 2 of the study, which enrolled 38 patients, the ORR was 32% (95% CI, 17.5%-48.7%), and all responses to sacituzumab govitecan were partial (n = 12) and lasted for a median duration of 5.6 months (95% CI, 2.8-13.3). After a median follow-up of 9.3 months (range, 0.5-30.6), the median progression-free survival (PFS) was 5.6 months (95% CI, 4.1-8.3) and the median overall survival (OS) was 13.5 months (95% CI, 7.6-15.6). Two-thirds of patients (68%) experienced a grade 3 or higher treatment-related adverse events (TRAEs); however, there were no treatment-related deaths.

“These data support further evaluation of sacituzumab govitecan—alone or in combination—in patients with metastatic urothelial carcinoma who progressed after prior CPI therapy,” lead investigator Daniel P. Petrylak, MD, said during a presentation of the results. “Sacituzumab govitecan had a manageable safety profile with no new safety signals and no treatment-related deaths.” Petrylak is a professor of medicine (medical oncology) and of urology, and chief of Genitourinary Oncology at Yale School of Medicine, in New Haven, Connecticut.

Sacituzumab govitecan received an accelerated approval from the FDA in April 2021 for patients with advanced urothelial cancer, based on findings from 112 patients in cohort 1 of the TROPHY-U-01 study. In this cohort, patients had progressed after platinum therapy and a CPI. In the data that led to the approval, the ORR was 27.7% (95% CI, 19.6%-36.9%), with a 5.4% complete response rate.2 In updated findings presented at the 2022 ASCO GU meeting,3 sacituzumab govitecan had an ORR of 28% (95% CI, 20.2%-37.6%) and 12-month PFS and OS rates of 14% and 45%, respectively.

For cohort 2 of the study, patients received sacituzumab govitecan at 10 mg/kg subcutaneously on days 1 and 8 of a 21-day cycle. The median age of patients in the study was 73 years (range, 41-87) and most were men (61%). ECOG status was evenly split between 0 and 1 (50% each) and two-thirds of patients (66%) had visceral metastases, with 29% of patients having liver metastasis at baseline. A third of patients had locoregional disease at baseline (34%).

The median number of prior therapies was 2 (range, 1-5), and half of patients (50%) had received platinum therapy as neoadjuvant or adjuvant therapy. Data on a prior CPI was missing for 1 patient; a majority of the remaining 97% of patients had received pembrolizumab (Keytruda) before entering the study (58%). Additionally, 18% of patients received prior enfortumab vedotin-ejfv (Padcev) and 3% had received erdafitinib (Balversa). The median time from last therapy to study drug administration was 1.6 months (range, 1-8). The median duration of last therapy was 4.2 months (range, 1-12), and the best response achieved was a complete response in 1 patient (3%) and a partial response in 6 (16%).

In addition to partial responses, an additional 13 patients had stable disease as their best overall response (34%). In roughly a quarter of these individuals, stable disease lasted for at least 6 months (n = 4; 11%). The clinical benefit rate, defined as responses plus stable disease for at least 6 months, was assessed as 42% (95% CI, 26.3%-59.2%). Slightly more than two-thirds of individuals (69%) experienced some degree of reduction in target lesion size.

“Responses were largely similar across prespecified subgroups,” Petrylak noted. “This was regardless of the number of prior anticancer therapies, although some of the subgroups were limited by very small patient numbers.”

The most common all-grade TRAEs were diarrhea (63%), alopecia (50%), nausea (47%), neutropenia (45%), fatigue (42%), anemia (37%), leukopenia (34%), and decreased appetite (26%). The most common grade 3 or higher TRAEs were neutropenia (34%), anemia (21%), leukopenia (18%), fatigue (18%), and diarrhea (16%). Additionally, 8% of patients experienced treatment-related febrile neutropenia, of which 2 cases were grade 3 and 1 was grade 4 in severity.

TRAEs led to treatment discontinuations for 18% of patients, and another 37% required a sacituzumab govitecan dose reduction. G-CSF was used as primary prophylaxis for 18% of patients and in 26% of patients for secondary prophylaxis. Commenting on the levels of myelotoxicity and the need for G-CSF, Petrylak said, “In practice, as well as in the trial, it was permitted that you could use primary prophylaxis, and I do, because this simply avoids the problem.”

The TROPHY-U-01 study consists of 6 arms assessing sacituzumab govitecan in various settings for patients with urothelial carcinoma. Cohorts 4, 5, and 6 examining the therapy as a first-line therapy remain open and are currently enrolling, Petrylak noted. Additionally, the phase 3 randomized TROPiCS-04 study (NCT04527991) of sacituzumab govitecan vs single-agent chemotherapy after progression of platinum therapy and a CPI is also ongoing, although no longer recruiting. Primary study completion is anticipated in August 2024.


  1. Petrylak DP, Tagawa ST, Jain RK, et al. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. J Clin Oncol. 2023;41(suppl 6):520. doi:10.1200/JCO.2023.41.6_suppl.520
  2. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed February 17, 2023.
  3. Tagawa ST, Balar AV, Petrylak DP, et al. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). J Clin Oncol. 2023;41(suppl 6):526. doi:10.1200/JCO.2023.41.6_suppl.526
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