Clinical trialPhase 3Kidney cancer

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

N Engl J Med · 20181096 patients (847 with intermediate or poor risk)

Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. N Engl J Med. 2018. 378:1277-1290

A newer report of this study has been published: Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial (2026)

Study type: Clinical trial
Study name: CheckMate 214
Phase: Phase 3
Design: Open-label randomised trial (1:1 ratio)
Sample size: 1096 patients (847 with intermediate or poor risk)
Source: N Engl J Med · 2018
Trial registration: NCT02231749

In plain words

In this study, people with advanced kidney cancer who had not yet had any treatment received either a combination of two immunotherapy drugs (nivolumab and ipilimumab) or sunitinib tablets, which were the standard treatment at the time. In patients whose disease was at intermediate or high risk, the immunotherapy combination helped them live longer and shrank tumours in more patients; in 9 of every 100 patients, the tumour disappeared completely on scans.

Key results

75% vs 60%

18-month overall survival (intermediate/poor risk)

Median survival: not reached vs 26.0 months; HR for death 0.63; P<0.001

42% vs 27%

Objective response (intermediate/poor risk)

P<0.001; complete response 9% vs 1%

11.6 vs 8.4 months

Median progression-free survival (intermediate/poor risk)

HR 0.82; P=0.03; not significant at the prespecified threshold of 0.009

46% vs 63%

Grade 3 or 4 treatment-related adverse events

Discontinuation due to adverse events: 22% vs 12%

Drugs in this study:Nivolumab (Opdivo)Ipilimumab (Yervoy)

Dose and schedule cards

Nivolumab + ipilimumab (CheckMate 214)

Advanced RCC, first line, IMDC intermediate or poor risk; SITC-preferred option for tumours with sarcomatoid featuresOn the page “Kidney cancer” · First-line regimens for advanced RCC

Advanced RCC, first line, IMDC intermediate or poor risk; SITC-preferred option for tumours with sarcomatoid features

Drug	Dose	Route	Schedule
Induction
Nivolumab	3 mg/kg	IV, 30-minute infusion (nivolumab first, then ipilimumab on the same day)	Day 1 every 3 weeks, 4 doses
Ipilimumab	1 mg/kg	IV, 30-minute infusion	Day 1 every 3 weeks, 4 doses
Maintenance
Nivolumab	240 mg (or 480 mg)	IV, 30-minute infusion	Every 2 weeks (480 mg dose: every 4 weeks)

Cycle length: Induction: every 21 days × 4; maintenance: every 14 or 28 days
Duration: 4 combination doses, then nivolumab monotherapy until progression or unacceptable toxicity

Per the FDA labels and the trial. Dose reduction of ipilimumab is not recommended; for toxicity, both drugs are withheld or permanently discontinued together. This combination should be given in experienced centres with the support of a multidisciplinary team.

On the page “Kidney cancer” · First-line regimens for advanced RCC

Advanced intermediate- or poor-risk renal cell carcinoma (CheckMate 214)

First lineOn the page “Ipilimumab (Yervoy)” · Other cancers, with nivolumab (FDA label, revised 08/2026)

First line

Drug	Dose	Route	Schedule
Combination: 4 doses
Nivolumab	3 mg/kg	IV, 30-minute infusion	Day 1 every 3 weeks (given first)
Ipilimumab	1 mg/kg	IV, 30-minute infusion	Same day, after nivolumab
Maintenance
Nivolumab	240 mg every 2 weeks or 480 mg every 4 weeks	IV, 30-minute infusion	After the 4 combination doses

Cycle length: 21 days, then 14 or 28 days
Duration: Combination 4 doses; nivolumab until progression or unacceptable toxicity

On the page “Ipilimumab (Yervoy)” · Other cancers, with nivolumab (FDA label, revised 08/2026)

Nivolumab + ipilimumab

Intermediate- and poor-risk advanced kidney cancerOn the page “Immunotherapy regimens in kidney cancer: pembrolizumab-axitinib, nivolumab-ipilimumab and adjuvant pembrolizumab”

Intermediate- and poor-risk advanced kidney cancer

Drug	Dose	Route	Schedule
Phase 1: 4 cycles
Nivolumab	3 mg/kg	IV	Day 1
Ipilimumab	1 mg/kg	IV	Day 1
Phase 2
Nivolumab	240 mg every 2 weeks or 480 mg every 4 weeks	IV	Day 1

Cycle length: Combination every 21 days; then nivolumab alone
Duration: Until progression

As in CheckMate 214.

Dose source:.

On the page “Immunotherapy regimens in kidney cancer: pembrolizumab-axitinib, nivolumab-ipilimumab and adjuvant pembrolizumab”

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 + ipilimumab

Induction: nivolumab 3 mg/kg IV (60-minute infusion) + ipilimumab 1 mg/kg IV (30-minute infusion) every 3 weeks for 4 doses. Maintenance: nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. Dose reductions of nivolumab and ipilimumab were not allowed; dose delays were allowed. 79% of patients received all 4 doses of ipilimumab.

2Sunitinib

Sunitinib 50 mg orally once daily for 4 weeks of each 6-week cycle (2 weeks off); dose reductions were allowed (made in 53% of patients).

Source of the regimen details: Full text of the paper (PMC5972549) and ClinicalTrials.gov NCT02231749

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 advanced or metastatic renal-cell carcinoma with a clear-cell component who had received no prior systemic therapy for advanced disease (except one adjuvant/neoadjuvant therapy without an anti-VEGF agent), with Karnofsky performance status of at least 70% and measurable disease (ClinicalTrials.gov). The primary endpoints were assessed in patients with IMDC intermediate or poor risk.

Endpoints

Co-primary endpoints (in intermediate-‎ or poor-risk patients): overall survival (alpha level 0.04), objective response rate (alpha level 0.001) and progression-free survival (alpha level 0.009).

Safety and side effects

Treatment-related adverse events of any grade occurred in 93% of the combination group (509 of 547) and 97% of the sunitinib group (521 of 535); grade 3 or 4 events in 46% vs 63%. Discontinuation because of treatment-related adverse events was 22% vs 12%. 8 deaths in the nivolumab + ipilimumab group and 4 deaths in the sunitinib group were attributed to treatment.

Clinical significance and place in guidelines

Based on this trial, in April 2018 the FDA approved the combination of ipilimumab and nivolumab for first-line treatment of intermediate-‎ or poor-risk advanced renal-cell carcinoma. The NCCN guideline (version 3.2022) lists this combination as a "preferred" option with category 1 evidence for intermediate and poor risk and as an "other recommended regimen" (category 2A) for favourable risk; the EAU 2022 guideline also gives it a strong recommendation for untreated patients with IMDC intermediate and poor risk.

Limitations

Open-label design; the primary endpoints were assessed only in intermediate-‎ and poor-risk patients, and in an exploratory analysis of favourable-risk patients the results favoured sunitinib; progression-free survival did not reach the significance threshold; the control (sunitinib) is no longer the standard first-line treatment.

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.