Chemotherapy for platinum-resistant advanced mUC yields poor objective response rates (ORR) and overall survival (OS). Nivolumab (NIVO) recently showed promising efficacy and safety in the CheckMate 032 phase I/II study (NCT01928394) in this setting. The current larger study, CheckMate 275 (NCT02387996), investigated efficacy and safety of NIVO in patients (pts) with mUC or surgically unresectable locally advanced UC that progressed after platinum-based chemotherapy.
In this open-label, single-arm, phase II study, pts received NIVO 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. The primary endpoint was ORR confirmed by blinded independent review committee (RECIST 1.1). Outcomes were evaluated in all treated pts and by tumor programmed death-1 ligand 1 (PD-L1) expression (≥1% and ≥5%; Dako PD-L1 PharmDx). Biomarkers were analyzed for association between response, UC subtype (by The Cancer Genome Atlas), and immune gene signature expression.
At 7 mo of median follow-up, 24.4% of pts remain on therapy. Confirmed ORR was 19.6% (95% CI 15.0–24.9), and 16.1% (95% CI 10.5–23.1) in pts with low to no PD-L1 expression (Table). Median duration of response was not reached, with responses ongoing in 76.9% of responders. Median progression-free survival was 2.00 mo (95% CI 1.87–2.63); median OS was 8.74 mo (95% CI 6.05–not estimable). Grade 3–4 treatment-related adverse events occurred in 18% of pts (grade 5, 1%), mainly fatigue and diarrhea (2% each). Basal 1 UC subtype had the highest proportion of responders and strongest interferon gamma (IFNγ) gene signature expression. Quality of life was stable over time.
In this large study in advanced/unresectable UC, NIVO had clinically meaningful efficacy and a manageable safety profile. Efficacy benefit of NIVO was seen across all PD-L1 subgroups.