Clinical trialPhase 3Kidney cancer

Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial

Ann Oncol · 2026651 patients

Motzer RJ, Escudier B, Burotto M, Powles T, Apolo AB, Bourlon MT, et al. Ann Oncol. 2026. 37:33-43

Study type: Clinical trial
Study name: CheckMate 9ER
Phase: Phase 3
Design: Randomised, open-label trial; median follow-up 5.6 years
Sample size: 651 patients
Source: Ann Oncol · 2026
Trial registration: NCT03141177

In plain words

In follow-up of more than 5 years, the combination of the immunotherapy drug nivolumab with the tablet cabozantinib helped patients with advanced kidney cancer typically live about 11 months longer than with sunitinib, and the tumour shrank in more than half of patients.

Key results

46.5 vs 35.5 months

Median overall survival

HR 0.79 (0.65–0.96); 60-month survival 40.9% vs 35.4%

16.4 vs 8.3 months

Median progression-free survival

HR 0.58 (0.49–0.70); 60-month progression-free survival 13.6% vs 3.6%

55.7% vs 27.4%

Objective response

Complete response 13.9% vs 4.6%

67.8% vs 55.0%

Grade 3–4 treatment-related adverse events

Drugs in this study:Nivolumab (Opdivo)

Dose and schedule cards

Nivolumab + cabozantinib (CheckMate 9ER)

Advanced RCC, first line, all IMDC risk groups; also an option in the papillary subtype (EAU)Each drug’s schedule in the tableOn the page “Kidney cancer” · First-line regimens for advanced RCC

Advanced RCC, first line, all IMDC risk groups; also an option in the papillary subtype (EAU)

Drug	Dose	Route	Schedule
Nivolumab	240 mg (or 480 mg)	IV, 30-minute infusion	Every 2 weeks (480 mg dose: every 4 weeks)
Cabozantinib	40 mg once daily	Oral, on an empty stomach (1 hour before or 2 hours after a meal)	Daily, continuously

Cycle schedule: Nivolumab every 2 weeks (or every 4 weeks with the 480 mg dose); cabozantinib daily and continuously
Duration: Nivolumab up to 2 years; cabozantinib until progression or unacceptable toxicity

Per the FDA labels and the trial. Cabozantinib dose reductions in this combination: 20 mg daily, then 20 mg every other day. ALT or AST >3 to 10 × ULN with bilirubin <2 × ULN: withhold both drugs until recovery to grade 0–1 (consider corticosteroids); >10 × ULN, or >3 × ULN with bilirubin ≥2 × ULN: permanently discontinue both. Liver enzymes should be monitored more frequently with this combination than with monotherapy. Stop cabozantinib 3 weeks before surgery (including dental surgery) and do not restart it for at least 2 weeks after major surgery; with strong CYP3A4 inhibitors, reduce the dose by 20 mg.

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

Advanced RCC, with cabozantinib (CheckMate 9ER)

First lineCycle length: 14 or 28 daysOn the page “Nivolumab (Opdivo)” · Combination regimens with chemotherapy or cabozantinib (FDA label, revised 05/2026)

First line

Drug	Dose	Route	Schedule
Continuous
Nivolumab	240 mg every 2 weeks or 480 mg every 4 weeks	IV, 30-minute infusion	Day 1
Cabozantinib	40 mg	Oral, fasting	Once daily

Cycle length: 14 or 28 days
Duration: Nivolumab until progression, unacceptable toxicity or a maximum of 2 years; cabozantinib until progression or toxicity

ALT/AST above 3 to 10 times ULN with bilirubin below 2 times: withhold both drugs until grade 0 to 1; above 10 times, or above 3 times with bilirubin 2 times or more: discontinue both permanently.

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 + cabozantinib

Nivolumab 240 mg IV every 2 weeks (maximum 2 years) + cabozantinib 40 mg orally once daily, until disease progression or unacceptable toxicity. Dose reduction was not allowed for nivolumab but was allowed for cabozantinib; discontinuation of each drug was assessed separately, and in case of toxicity related to one drug, the other drug could be continued.

2Sunitinib

Sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off (6-week cycle), until progression or unacceptable toxicity; dose reduction was allowed.

Source of the regimen details: Abstract of the paper (PubMed), full text of the primary CheckMate 9ER paper (NEJM 2021; PMC8436591) and ClinicalTrials.gov NCT03141177

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 (not amenable to curative surgery or radiotherapy) or metastatic renal cell carcinoma with a clear-cell component, without previous systemic therapy, in all IMDC risk groups, with a Karnofsky performance status of at least 70 and measurable disease per RECIST 1.1; patients with active brain metastases or active autoimmune disease were excluded.

Endpoints

Primary: progression-free survival by blinded independent central review; secondary: overall survival, objective response and safety.

Safety and side effects

Treatment-related adverse events of any grade were 97.5% versus 93.1% and grade 3–4 67.8% and 55.0%, respectively; from a median follow-up of 32.9 months onwards no new deaths due to drug toxicity occurred.

Clinical significance and place in guidelines

The final analysis confirms the overall survival and progression-free survival benefit with long follow-up (overall survival HR 0.79 versus 0.60 in the first report).

Limitations

The trial is open-label; subsequent treatments after progression may affect overall survival.

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.