Final CheckMate 9ER Results Confirm Long-Term Benefit of Nivolumab With Cabozantinib in aRCC

Previous results of the phase III CheckMate 9ER trial showed that nivolumab combined with cabozantinib provided substantial benefits in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) over sunitinib alone for patients with untreated advanced renal cell carcinoma (aRCC).

Final results from the study and its long-term follow-up (5 years or longer) were presented at the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium along with updated efficacy results of the study’s intent-to-treat population, risk based on International Metastatic RCC Database Consortium (IMDC) criteria, and safety.

In CheckMate 9ER, patients with aRCC were randomized to receive first-line treatment with 240 mg of nivolumab every two weeks plus 40 mg of cabozantinib (N+C) daily or 50 mg of sunitinib alone daily (administered for four weeks in each six-week cycle) until disease progression or unacceptable toxicity occurred, with a maximum duration of two years for nivolumab.

The study’s primary endpoint was PFS based on RECIST v1.1 as determined by blinded independent central review (BICR), and secondary endpoints included OS, ORR based on RECIST v1.1 as determined by BICR, and safety.

The median follow-up was 67.6 months (range, 60.2–80.2). In the intent-to-treat population, N+C was administered to 323 patients, and 328 patients received sunitinib. PFS favored N+C over sunitinib (hazard ratio [HR], 0.58; 95% CI, 0.49-0.70). The median PFS was 16.4 (range, 12.5–19.3) months for N+C and 8.3 months (range, 7.0–9.7) for sunitinib, with 60-month PFS rates of 13.6% and 3.6%, respectively.

OS results were also in favor of N+C over sunitinib (HR, 0.79; 95% CI, 0.65-0.96). The median OS of N+C was 46.5 months (range, 40.6–53.8) over 35.5 months (range, 29.2–42.8) for sunitinib, and the 60-month OS rates were 40.9% and 35.4%, respectively.

The ORR was higher with N+C compared with sunitinib (55.7% vs 27.4%), with complete response rates of 13.9% versus 4.6%, respectively. Duration of response at 60 months was 22.0% with N+C and 10.0% with sunitinib. Among all treated patients (320 per arm), treatment-related adverse events of any grade (including grade ≥3) occurred in 97.5% (67.8%) of patients treated with N+C and 93.1% (55.3%) of patients treated with sunitinib. No new treatment-related deaths have been reported since the last database lock. Additional subgroup analyses will be presented.

In this final follow-up report of CheckMate9ER, a long-term efficacy benefit was seen with N+C over sunitinib, with no new safety signals. These results continue to support the use of N+C as a standard of care for patients with previously untreated aRCC.