Background
Multicenter single-arm phase II trial of 270 patients with metastatic or unresectable urothelial carcinoma that progressed after at least one platinum-based regimen.
Interventions and follow up
Regimen: Nivolumab 3 mg/kg IV q2wk until progression or unacceptable toxicity
Primary endpoint: Objective response rate (ORR) by RECIST v1.1
Median follow up: 7.0 mo
Primary endpoint: Objective response rate (ORR) by RECIST v1.1
Median follow up: 7.0 mo
Results
ORR (overall): 19.6% (CR 2%, PR 17%)
ORR (PD-L1 ≥5%): 28.4%
ORR (PD-L1 ≥1%): 23.8%
ORR (PD-L1 <1%): 16.1%
ORR (PD-L1 ≥5%): 28.4%
ORR (PD-L1 ≥1%): 23.8%
ORR (PD-L1 <1%): 16.1%
Adverse events
Grade 3 treatment-related events: Fatigue 2%; diarrhea 2%
Grade 1-2 events: Fatigue 15%; pruritus 9%; decreased appetite 8%; hypothyroidism 8%; diarrhea 7%
Grade 1-2 events: Fatigue 15%; pruritus 9%; decreased appetite 8%; hypothyroidism 8%; diarrhea 7%
Conclusions
Nivolumab produced durable responses across PD-L1 subgroups with a manageable safety profile in previously treated metastatic or unresectable urothelial carcinoma.
Key Limitations
Single-arm, non-comparative design with short follow-up and ORR as primary endpoint, precluding survival comparison. Higher response with greater PD-L1 expression but activity seen across subgroups.
Clinical Context
CheckMate 275 supported FDA accelerated approval of nivolumab for platinum-refractory advanced urothelial carcinoma. ASCO/ESMO recognize checkpoint inhibitors in this setting; second-line standards have since evolved with enfortumab vedotin and earlier immunotherapy use.