Background
Phase III, open-label RCT. 608 cisplatin-eligible patients with previously untreated unresectable or metastatic urothelial carcinoma (mUC), ECOG PS 0–1. Nivolumab added to cisplatin + gemcitabine chemotherapy tested in the first-line mUC cisplatin-eligible population. Compared against chemotherapy alone as standard of care prior to EV + pembrolizumab era.
Interventions and follow up
Arm A: Nivolumab 360mg IV q3wk + cisplatin 70mg/m² D1 + gemcitabine 1000mg/m² D1, D8 q3wk × up to 6 cycles, then nivolumab maintenance 480mg IV q4wk
Arm B: Cisplatin 70mg/m² D1 + gemcitabine 1000mg/m² D1, D8 q3wk × up to 6 cycles
Primary endpoint: OS
mFollow up: 33.6 mo
Arm B: Cisplatin 70mg/m² D1 + gemcitabine 1000mg/m² D1, D8 q3wk × up to 6 cycles
Primary endpoint: OS
mFollow up: 33.6 mo
Results
OS: 21.7 vs 18.9 mo, HR 0.78, P=.028
PFS: 7.9 vs 7.6 mo, HR 0.72, P=.001
ORR: 57.5% vs 43.1%
CR rate: 21.7% vs 11.8%
PFS: 7.9 vs 7.6 mo, HR 0.72, P=.001
ORR: 57.5% vs 43.1%
CR rate: 21.7% vs 11.8%
Adverse events
Overall grade ≥3: 61.8% vs 51.7%
Immune-mediated (any grade): 30.0% vs 4.5%
Endocrine: hypothyroidism (any grade) 14.5% vs 0.3%
GI: colitis grade ≥3 3.3% vs 0.7%
Pulmonary: pneumonitis grade ≥3 1.0% vs 0.3%
Renal: renal toxicity grade ≥3 5.3% vs 3.3%
Discontinuation due to AEs: 16.8% vs 7.0%
Immune-mediated (any grade): 30.0% vs 4.5%
Endocrine: hypothyroidism (any grade) 14.5% vs 0.3%
GI: colitis grade ≥3 3.3% vs 0.7%
Pulmonary: pneumonitis grade ≥3 1.0% vs 0.3%
Renal: renal toxicity grade ≥3 5.3% vs 3.3%
Discontinuation due to AEs: 16.8% vs 7.0%
Conclusions
Nivolumab + cisplatin/gemcitabine significantly improved OS and PFS versus chemotherapy alone in cisplatin-eligible first-line mUC, establishing a chemo-IO combination option in this setting. The 2.8-month improvement in median OS and HR of 0.78 are statistically significant but modest in absolute terms.
Key Limitations
Key Limitations: The OS benefit of 2.8 months is modest, and the HR of 0.78 compares unfavorably to the transformative HR of 0.47 seen with EV + pembrolizumab (EV-302). CheckMate 901 is restricted to cisplatin-eligible patients only — carboplatin-ineligible patients were not enrolled. The emergence of EV + pembrolizumab (EV-302) as a superior standard regardless of cisplatin eligibility has significantly limited the clinical role of CheckMate 901's combination in current practice. Maintenance nivolumab adds cost and toxicity.
Clinical Context
CheckMate 901 established nivolumab + gem-cis as FDA-approved (2024) first-line mUC in cisplatin-eligible patients. However, EV + pembrolizumab (EV-302, also 2024 approval) is now broadly preferred given its superior OS benefit (HR 0.47 vs 0.78) across all cisplatin eligibility strata. CheckMate 901 may still be relevant in settings where EV + pembrolizumab access is limited, or in clinical scenarios where the Nectin-4/ADC toxicity profile (neuropathy, skin toxicity, hyperglycemia) is prohibitive.
References
References: van der Heijden MS et al, NEJM 2023