Clinical trialPhase 3Bladder cancer

Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma

N Engl J Med · 2023608 patients (304 in each group)

van der Heijden MS, Sonpavde G, Powles T, et al. N Engl J Med. 2023. 389:1778-1789

Study type: Clinical trial
Study name: CheckMate 901
Phase: Phase 3
Design: Randomised, open-label, multinational trial
Sample size: 608 patients (304 in each group)
Source: N Engl J Med · 2023
Trial registration: NCT03036098

In plain words

In patients with advanced bladder cancer whose kidneys work well enough to receive cisplatin, adding the immunotherapy drug nivolumab to standard chemotherapy increased median survival by about 3 months (from 19 to 22 months) and nearly doubled complete responses (tumours disappearing on scans). Today this combination is an alternative for when the preferred treatment (enfortumab vedotin + pembrolizumab) is not possible.

Key results

21.7 vs 18.9 months

Median overall survival

HR for death 0.78 (95% CI 0.63–0.96); P=0.02; median follow-up 33.6 months

7.9 vs 7.6 months

Median progression-free survival

HR 0.72 (95% CI 0.59–0.88); P=0.001; 12-month progression-free survival 34.2% vs 21.8%

57.6% (21.7%) vs 43.1% (11.8%)

Objective response (complete response)

Median duration of complete response 37.1 vs 13.2 months

61.8% vs 51.7%

Grade 3 or higher adverse events

As reported in the abstract of the paper

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Gemcitabine (Gemzar)Nivolumab (Opdivo)

Dose and schedule cards

Nivolumab + gemcitabine-cisplatin (CheckMate 901)

First line, cisplatin-eligible (GFR ≥60 mL/min), ECOG 0 to 1; recurrence at least 12 months after perioperative chemotherapyOn the page “Bladder cancer” · Advanced or metastatic disease: first line

First line, cisplatin-eligible (GFR ≥60 mL/min), ECOG 0 to 1; recurrence at least 12 months after perioperative chemotherapy

Drug	Dose	Route	Schedule
Combination: up to 6 cycles of 21 days
Nivolumab	360 mg	IV over 30 minutes	Day 1
Cisplatin	70 mg/m²	IV	Day 1
Gemcitabine	1000 mg/m²	IV	Days 1 and 8
Maintenance
Nivolumab	480 mg (or 240 mg every 2 weeks)	IV over 30 minutes	Every 4 weeks

Cycle length: Every 21 days, then every 28 days
Duration: Nivolumab until progression, toxicity or up to 2 years from the first dose

Per the FDA label and the trial. In the trial, patients who discontinued only cisplatin received gemcitabine-carboplatin for the remaining cycles.

On the page “Bladder cancer” · Advanced or metastatic disease: first line

Unresectable or metastatic urothelial carcinoma, with cisplatin and gemcitabine (CheckMate 901)

First lineOn the page “Nivolumab (Opdivo)” · Combination regimens with chemotherapy or cabozantinib (FDA label, revised 05/2026)

First line

Drug	Dose	Route	Schedule
Combination: up to 6 cycles
Nivolumab	360 mg	IV, 30-minute infusion	Day 1 every 3 weeks (given first)
Cisplatin + gemcitabine	As per those drugs' labels	IV	Same day, after nivolumab
Monotherapy after the combination
Nivolumab	240 mg every 2 weeks or 480 mg every 4 weeks	IV, 30-minute infusion	Starting after the combination doses

Cycle length: 21 days, then 14 or 28 days
Duration: Monotherapy until progression, unacceptable toxicity or 2 years from the first dose

On the page “Nivolumab (Opdivo)” · Combination regimens with chemotherapy or cabozantinib (FDA label, revised 05/2026)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Nivolumab + gemcitabine-cisplatin

Nivolumab 360 mg IV + cisplatin 70 mg/m² IV day 1 + gemcitabine 1000 mg/m² IV days 1 and 8, every 21 days for up to 6 cycles; then nivolumab 480 mg IV every 4 weeks until progression, unacceptable toxicity or a maximum of 2 years from the first dose. Patients who stopped cisplatin only could receive gemcitabine-carboplatin for the remaining cycles (up to 6 cycles) (16.1% received at least one dose of carboplatin).

2Gemcitabine-cisplatin alone

Cisplatin 70 mg/m² day 1 + gemcitabine 1000 mg/m² days 1 and 8, every 21 days for up to 6 cycles; switching to gemcitabine-carboplatin after stopping cisplatin was allowed (14.9%).

Source of the regimen details: Full text of the paper (PMC12314471) and the FDA label for OPDIVO (DailyMed, Clinical Studies section CHECKMATE-901: cisplatin 70 mg/m² day 1 and gemcitabine 1000 mg/m² days 1 and 8)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with unresectable or metastatic urothelial carcinoma (renal pelvis, ureter, bladder or urethra) without previous systemic chemotherapy for advanced disease, with measurable disease, ECOG performance status 0 or 1 and eligible for cisplatin (including a glomerular filtration rate of 60 mL per minute or more).

Endpoints

Primary endpoints: overall survival and progression-free survival (by blinded independent central review). Objective response and safety were exploratory endpoints.

Safety and side effects

Grade 3 or higher adverse events of any cause 76.6% in the combination group versus 67.7% with gemcitabine-cisplatin; grade 3 or higher treatment-related adverse events 61.8% versus 51.7% (the figure given in the abstract).

Clinical significance and place in guidelines

On 6 March 2024 the FDA approved nivolumab with cisplatin and gemcitabine for first-line treatment of adults with unresectable or metastatic urothelial carcinoma. EAU guideline 2025: if enfortumab vedotin is contraindicated or unavailable in a cisplatin-eligible patient, cisplatin/gemcitabine with nivolumab should be considered (strong recommendation).

Limitations

Open-label design; only cisplatin-eligible patients (about half of patients with bladder cancer are not eligible); the difference in median progression-free survival was small; the control group did not systematically receive maintenance avelumab.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.