Final CheckMate 9ER data show long-term efficacy of nivolumab/cabozantinib in RCC

Final data from the phase 3 CheckMate 9ER (NCT03141177) study evaluating nivolumab (Opdivo) plus cabozantinib (Cabometyx) vs sunitinib (Sutent) showed that the combination was safe and yielded long-term efficacy in patients with previously untreated advanced renal cell carcinoma (RCC).¹

The findings were presented at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.

Robert J. Motzer, MD

“Nivolumab plus cabozantinib showed significant efficacy benefits vs sunitinib for patients with previously untreated advanced RCC in the primary analysis of the phase 3 CheckMate 9ER trial,”² said presenting author Robert J. Motzer, MD, section head of Kidney Cancer, Genitourinary Oncology Service and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York, New York. Previously reported data indicated that median progression-free survival (PFS) was 16.6 months in the nivolumab plus cabozantinib arm vs 8.3 months in the sunitinib arm (HR=0.51, 95% CI, 0.41-0.64; P < .001). Median overall survival (OS) was not reached in either arm (HR=0.60, 98.89% CI, 0.40-0.89; P = .001). Objective response rate (ORR) was 55.7% in the nivolumab plus cabozantinib arm vs 27.1% in the sunitinib arm (P < .001). At ASCO GU, Motzer presented final efficacy and safety data from CheckMate 9ER at a median follow-up of 67.6 months.

CheckMate 9ER included a total of 651 patients with previously untreated advanced or metastatic RCC, a clear cell component, and any International Metastatic RCC Database Consortium (IMDC) risk group. Patients were randomly assigned 1:1 to either nivolumab 240 mg intravenously once every 2 weeks and cabozantinib 40 mg once per day by mouth or sunitinib 50 mg once per day by mouth on a cycle of 4 weeks on and 2 weeks off. Primary end point was PFS per blinded independent central review (BICR). Key secondary end points included OS, ORR per BICR, and safety.

A total of 323 patients received nivolumab plus cabozantinib and 328 patients received sunitinib. In terms of baseline patient characteristics, the median age was 62 (range, 29-90 years) years in the nivolumab plus cabozantinib arm and 61 (range, 28-86 years) years in the sunitinib arm. Sixty-nine percent of the nivolumab plus cabozantinib arm had undergone prior nephrectomy vs 71% of the sunitinib arm. IMDC risk group was favorable, intermediate, or poor in 23%, 58%, and 19%, respectively, in the nivolumab plus cabozantinib arm and 22%, 57%, and 21% in the sunitinib arm.

Motzer reported that median PFS was 16.4 months in the nivolumab plus cabozantinib arm (95% CI, 12.5-19.3) vs 8.3 months in the sunitinib arm (95% CI, 7.0-9.7) (HR=0.58, 95% CI, 0.49-0.70). Median OS in the intent-to-treat (ITT) population was 46.5 months in the nivolumab plus cabozantinib arm (95% CI, 40.6-53.8) vs 35.5 months in the sunitinib arm (95% CI, 29.2-42.8) (HR=0.79, 95% CI, 0.65-0.96).

ORR per BICR in the ITT population was 55.7% in the nivolumab plus cabozantinib arm (95% CI, 50.1-61.2) and 27.4% in the sunitinib arm (95% CI, 22.7-32.6).

Median duration of response per BICR in the ITT population was 22.0% months in the nivolumab plus cabozantinib arm (95% CI, 18.0-25.2) vs 15.2 months in the sunitinib arm (95% CI, 10.9-19.3).

The investigators also evaluated a subgroup of patients with IMDC favorable-risk disease. In these patients, median PFS per BICR was 21.4 months in the nivolumab plus cabozantinib arm and 12.8 months in the sunitinib arm (95% CI, 9.4-16.6) (HR=0.67, 95% CI, 0.46-0.97). Median OS in this subgroup was 53.7 months in the nivolumab plus cabozantinib arm (95% CI, 40.8-70.7) and 58.9 months in the sunitinib arm (95% CI, 46.1-not evaluable) (HR=1.08, 95% CI, 0.70-1.66). ORR per BICR in this subgroup was 66.2% in the nivolumab plus cabozantinib arm and 43.1% in the sunitinib arm.

Regarding patients with IMDC intermediate/poor-risk disease, median PFS per BICR was 15.4 months in the nivolumab plus cabozantinib arm (95% CI, 11.1-18.6) and 7.1 months in the sunitinib arm (95% CI, 5.7-8.9). Median OS in this subgroup was 43.9 months in the nivolumab plus cabozantinib arm (95% CI, 34.9-53.0) and 29.2 months in the sunitinib arm (95% CI, 23.7-36.0) (HR=0.74, 95% CI, 0.60-0.92). ORR per BICR in this subgroup was 52.6% in the nivolumab plus cabozantinib arm and 23.0% in the sunitinib arm.

A total of 299 (93%) patients in the nivolumab plus cabozantinib arm discontinued study treatment vs 305 (95%) in the sunitinib arm. In addition, 129 (43%) patients received subsequent systemic therapy in nivolumab plus cabozantinib arm vs 168 (55%) patients in the sunitinib arm.

Regarding safety, any-grade adverse events (AEs) occurred in 98% of patients in the nivolumab plus cabozantinib arm vs 93% in the sunitinib arm. Grade 3-4 AEs occurred in 68% of patients in the nivolumab plus cabozantinib arm vs 55% in the sunitinib arm. Treatment-related AEs observed in both arms included diarrhea, palmar-plantar erythrodysesthesia, hypertension, fatigue, hypothyroidism, nausea, mucosal inflammation, stomatitis, anemia, dysgeusia, thrombocytopenia, decreased appetite, increased aspartate aminotransferase, increased alanine aminotransferase, and rash.

“These results continue to support [nivolumab plus cabozantinib] as a standard of care for previously untreated advanced RCC,” Motzer said in his concluding remarks.

REFERENCES

1. 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. J Clin Oncol. 2025;43(suppl 5). Abstract 439. doi:10.1200/JCO.2025.43.5_suppl.439

2. Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829-841. doi:10.1056/NEJMoa2026982