A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
Summary
The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma
Timeline
- Start
- 2017-07-23
- Primary completion
- 2020-02-12
- Completion
- 2026-01-16
Outcome
Met primary endpoint
registry MEDIAN Treatment A: 16.59 (12.45 to 24.94) Months MEDIAN Treatment C: 8.31 (6.97 to 9.69) Months NCT03141177 ↗
registry analysis (superiority test); Treatment A vs Treatment C; p <0.0001; Hazard Ratio (HR) 0.51 (95% CI 0.41 to 0.64); Stratified Log-Rank NCT03141177 ↗
release “CheckMate -9ER trial met its key efficacy measures of progression-free survival as well as overall survival” ipsen.com ↗
release “met its primary endpoint of progression-free survival (PFS) at final analysis” exelixis.com ↗
release “trial evaluating nivolumab in combination with cabozantinib compared to sunitinib in previously untreated advanced or metastatic RCC, met its primary endpoint of progression-free survival” exelixis.com ↗
release “met its primary endpoint of progression-free survival (PFS) at final analysis” ipsen.com ↗
release “The CheckMate -9ER data demonstrate meaningful efficacy benefits with nivolumab plus cabozantinib, which significantly improved overall survival and doubled progression-free survival and objective response rate” exelixis.com ↗
release “median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone” exelixis.com ↗
release “In CheckMate -9ER, OPDIVO in combination with CABOMETYX demonstrated significant improvements across all efficacy endpoints” exelixis.com ↗
release “CheckMate -9ER phase 3 pivotal trial, which met its primary endpoint” exelixis.com ↗
release “CheckMate -9ER trial (Abstract #308) with a median follow-up of two years (23.5 months), Cabometyx® in combination with Opdivo® continued to show superior progression-free survival” ipsen.com ↗
release “the combination doubled median PFS (17.0 months vs. 8.3 months, respectively; HR 0.52; 95% CI: 0.43 to 0.64), the trial’s primary endpoint, compared to sunitinib.” ipsen.com ↗
release “CheckMate -9ER trial, in which Cabometyx® (cabozantinib) in combination with Opdivo® (nivolumab) doubled progression-free survival” ipsen.com ↗
release “median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone” ipsen.com ↗
release “PFS benefits, the primary endpoint of the study, were also maintained” ipsen.com ↗
release “Median PFS was almost doubled at 16.6 versus 8.4 months for Cabometyx in combination with nivolumab versus sunitinib respectively” ipsen.com ↗
release “Opdivo in combination with CABOMETYX reduced the risk of death by 23% in the first-line treatment of advanced renal cell carcinoma vs. sunitinib” exelixis.com ↗
release “PFS (primary endpoint): PFS continued to favor Opdivo plus CABOMETYX” exelixis.com ↗
release “CABOMETYX in combination with Opdivo improved progression-free survival” exelixis.com ↗
release “compared to sunitinib in previously untreated advanced or metastatic renal cell carcinoma (RCC), met its primary endpoint of progression-free survival (PFS)” bms.com ↗
release “Phase 3 CheckMate -9ER trial, which demonstrated superior efficacy with Opdivo in combination with Cabometyx versus sunitinib across three key endpoints: progression-free survival (PFS)” bms.com ↗
release “PFS: Opdivo in combination with Cabometyx doubled median PFS” bms.com ↗
Publications
- Viray H, M Mantia C, Jegede OA, Atkins MB, Rosenblatt L, Choueiri TK, McDermott DF, Regan MM. Partitioned overall survival: comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma. J Immunother Cancer. 2026 Jan 30;14(1):e013546. doi: 10.1136/jitc-2025-013546.
- Grimm MO, Karim E, Kapetanakis V, Lothgren M, Ogareva A, Shukla P, Truscott J, Porta C. Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy. Oncol Ther. 2026 Mar;14(1):253-268. doi: 10.1007/s40487-025-00393-9. Epub 2025 Nov 15.
- Motzer RJ, Escudier B, Burotto M, Powles T, Apolo AB, Bourlon MT, Shah AY, Porta C, Suarez C, Barrios CH, Richardet M, Gurney H, Kessler ER, Tomita Y, Bedke J, Scheffold C, Askelson M, Panzica J, Zhang J, van Kooten Losio M, Choueiri TK. Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial. Ann Oncol. 2026 Jan;37(1):33-43. doi: 10.1016/j.annonc.2025.09.006. Epub 2025 Sep 23.
- Cella D, Motzer RJ, Suarez C, Blum SI, Ejzykowicz F, Hamilton M, Wallace JF, Simsek B, Zhang J, Ivanescu C, Choueiri TK, Apolo AB. Plain language summary of quality of life in CheckMate 9ER: Cabozantinib plus nivolumab in advanced renal cell carcinoma. Future Oncol. 2025 Jan;21(2):181-194. doi: 10.1080/14796694.2024.2415786. Epub 2024 Oct 25.
- Powles T, Burotto M, Escudier B, Apolo AB, Bourlon MT, Shah AY, Suarez C, Porta C, Barrios CH, Richardet M, Gurney H, Kessler ER, Tomita Y, Bedke J, George S, Scheffold C, Wang P, Fedorov V, Motzer RJ, Choueiri TK. Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial. ESMO Open. 2024 May;9(5):102994. doi: 10.1016/j.esmoop.2024.102994. Epub 2024 Apr 20.
- Petersohn S, McGregor B, Klijn SL, May JR, Ejzykowicz F, Kurt M, Dyer M, Malcolm B, Branchoux S, Nickel K, George S, Kroep S. Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma. J Comp Eff Res. 2023 Aug;12(8):e230004. doi: 10.57264/cer-2023-0004. Epub 2023 Jul 11.
- Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
- Tran BD, Li J, Ly N, Faggioni R, Roskos L. Cabozantinib exposure-response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2023 Feb;91(2):179-189. doi: 10.1007/s00280-022-04500-9. Epub 2023 Jan 10.
- Apolo AB, Powles T, Escudier B, Burotto M, Zhang J, Simsek B, Scheffold C, Motzer RJ, Choueiri TK. Nivolumab plus ipilimumab plus cabozantinib triplet combination for patients with previously untreated advanced renal cell carcinoma: Results from a discontinued arm of the phase III CheckMate 9ER trial. Eur J Cancer. 2022 Dec;177:63-71. doi: 10.1016/j.ejca.2022.09.020. Epub 2022 Oct 4.
- Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suarez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):888-898. doi: 10.1016/S1470-2045(22)00290-X. Epub 2022 Jun 7.
- Cella D, Motzer RJ, Suarez C, Blum SI, Ejzykowicz F, Hamilton M, Wallace JF, Simsek B, Zhang J, Ivanescu C, Apolo AB, Choueiri TK. Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):292-303. doi: 10.1016/S1470-2045(21)00693-8. Epub 2022 Jan 12.
- Hamuro L, Hu Z, Passarell J, Barcomb H, Zhang J, Goldstein S, Bello A, Roy A, Zhu L. Exposure-Response Analysis to Support Nivolumab Once Every 4 Weeks Dosing in Combination with Cabozantinib in Renal Cell Carcinoma. Clin Cancer Res. 2022 Apr 14;28(8):1603-1613. doi: 10.1158/1078-0432.CCR-21-3149.
- Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juarez VM, Hsieh JJ, Basso U, Shah AY, Suarez C, Hamzaj A, Goh JC, Barrios C, Richardet M, Porta C, Kowalyszyn R, Feregrino JP, Zolnierek J, Pook D, Kessler ER, Tomita Y, Mizuno R, Bedke J, Zhang J, Maurer MA, Simsek B, Ejzykowicz F, Schwab GM, Apolo AB, Motzer RJ; CheckMate 9ER Investigators. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841. doi: 10.1056/NEJMoa2026982.
- Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Cabozantinib | Small molecule | 40 mg | Oral |
| Subject | Ipilimumab | Monoclonal antibody | 1 mg/kg | — |
| Subject | Nivolumab | Monoclonal antibody | 240 mg | Intravenous |
| Comparator | Sunitinib | Small molecule | 50 mg | Oral |