Background
Single-arm, open-label phase 2 basket trial (Cohort 1). 113 patients with locally advanced or metastatic urothelial carcinoma who had received prior platinum-based chemotherapy AND a checkpoint inhibitor (PD-1/PD-L1 inhibitor). Sacituzumab govitecan (SG; anti-Trop-2 ADC coupled to SN-38, an active irinotecan metabolite) tested in platinum- and IO-refractory UC — the same ADC approved in TNBC (ASCENT).
Interventions and follow up
Arm A: Sacituzumab govitecan 10mg/kg IV D1, D8 q3wk
Arm B: Not applicable — single-arm study
Primary endpoint: Objective response rate (ORR)
mFollow up: 9.1 mo
Arm B: Not applicable — single-arm study
Primary endpoint: Objective response rate (ORR)
mFollow up: 9.1 mo
Results
ORR: 27.4% (95% CI 19.3–36.8%)
CR rate: 5.3%
mPFS: 5.4 mo
mOS: 10.9 mo
CR rate: 5.3%
mPFS: 5.4 mo
mOS: 10.9 mo
Adverse events
Overall grade ≥3: 63.4%
Hematologic: neutropenia grade ≥3 34.5% (most common); leukopenia grade ≥3 17.7%; anemia grade ≥3 13.3%; febrile neutropenia 6.2% — G-CSF recommended
GI: diarrhea grade ≥3 10.6% — SN-38 class effect; nausea (any grade) 64.6%
Dermatologic: alopecia (any grade) 46.9%
Discontinuation due to AEs: 10.6%
Hematologic: neutropenia grade ≥3 34.5% (most common); leukopenia grade ≥3 17.7%; anemia grade ≥3 13.3%; febrile neutropenia 6.2% — G-CSF recommended
GI: diarrhea grade ≥3 10.6% — SN-38 class effect; nausea (any grade) 64.6%
Dermatologic: alopecia (any grade) 46.9%
Discontinuation due to AEs: 10.6%
Conclusions
Sacituzumab govitecan demonstrated clinically meaningful activity with ORR ~27% in heavily pretreated post-platinum and post-IO mUC, establishing Trop-2 as a therapeutic target in this population and SG as a viable later-line option.
Key Limitations
Key Limitations: Non-randomized single-arm phase 2 design — no direct comparison to other agents. ORR of 27% requires contextualization: chemotherapy in this population achieves ORR 10–15%, so the absolute benefit is meaningful but not transformative. Grade ≥3 neutropenia (34.5%) and diarrhea (10.6%) are significant and require careful patient selection and prophylactic G-CSF. The UGT1A1*28 polymorphism (poor SN-38 metabolizers) is associated with higher toxicity. The role of SG in the EV-302 era — where patients will have received EV+pembro first-line — is being explored in subsequent cohorts and ongoing trials.
Clinical Context
FDA approved sacituzumab govitecan for locally advanced or metastatic UC in 2021 based on TROPHY-U-01. SG provides a Trop-2-directed ADC option distinct from enfortumab vedotin (Nectin-4 target) in the UC ADC landscape. The two ADCs have non-overlapping targets and toxicity profiles, enabling sequential use. In the EV+pembro first-line era, subsequent ADC options (SG, erdafitinib) will be deployed post-EV. UGT1A1 genotyping may guide dosing in high-risk patients.
References
References: Tagawa ST et al, JCO 2021