In the final follow-up analysis of the phase 3 CheckMate 9ER trial, there was a long-term efficacy benefit with nivolumab plus cabozantinib compared with sunitinib among patients with advanced renal cell carcinoma (RCC).

These results were first presented by Robert Motzer, MD, Memorial Sloan Kettering Cancer Center, New York, NY, at the 2025 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

In this phase 3 trial, patients were randomized to receive either 240 mg nivolumab every 2 weeks plus 40 mg cabozantinib daily (n = 323) or 50 mg sunitinib daily (n = 328) until disease progression or unacceptable toxicity, or 2 years maximum for nivolumab. The primary end point of this trial was progression-free survival (PFS) by blinded independent central review. Secondary end points included overall survival (OS), and objective response rate (ORR) by blinded independent central review, and safety. A previously reported, there was a benefit seen for PFS, OS, and ORR with the combination arm vs the sunitinib arm.

With a median follow-up of 67.6 months, the PFS in the intention-to-treat population favored the nivolumab plus cabozantinib arm over the sunitinib arm, with a hazard ratio of 0.58. The median PFS was 16.4 months with combination vs 8.3 with sunitinib, and the 60-month PFS rates were 13.6% and 3.6% respectively. OS also favored the combination over sunitinib with a hazard ratio of 0.79. The median OS was 46.5 months with the combination and 35.5 with sunitinib, and the 50-month OS rates were 40.9% and 35.4% respectively. The ORR was 55.7% in the nivolumab plus cabozantinib arm vs 27.4% in the sunitinib arm, with complete response rates of 13.9% and 4.6% respectively. At 60 months, the duration of response was 22.0% with the combination and 10.0% with sunitinib.

Among all treated patients, grade ≥3 treatment-related adverse events occurred in 67.8% of patients in the nivolumab plus cabozantinib arm and 55.3% in the sunitinib arm. There were no new deaths due to toxicities with the study treatment since the last analysis.
 
Dr Motzer et al, concluded that these results “continued to support [nivolumab plus cabozantinib] as a standard of care” for previously untreated patients with advanced RCC.

Source:

Motzer R, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N + C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial. Presented at the 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 439