CABOMETYX® (cabozantinib) aRCC data in combination with OPDIVO® (nivolumab)
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1L aRCC Combination Treatment
See the results from the CheckMate-9ER study - including efficacy, safety, and patient-reported quality of life data.

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CheckMate-9ER: a phase 3, randomized, head-to-head trial.1,2
An open-label trial vs sunitinib in patients with previously untreated aRCC.1,2
1:1 randomization2,3 (N=651) Patients had previously untreated aRCC with a clear-cell component2,3 Enrollment of patients with favorable IMDC risk score limited to ~25% of population3,4 |
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Treatment until disease progression or unacceptable toxicity1* | ||||
Primary endpoint1,2 PFS† |
Secondary endpoints1,2 OS ORR† Safety |
Exploratory endpoint3‡ HRQoL |
- Excluded patients with autoimmune disease or other medical conditions requiring systemic immunosuppression1
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Median follow-up was 18.1 months, with extended median follow-ups of 23.5 months (range: 16.0-36.0 months) and 32.9 months (range: 25.4-45.4 months)2,3,5
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32.9 month median follow-up data was a pre-planned analysis that occurred after observation of 271 events1
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Tumor assessments were performed at baseline, after randomization at Week 12, then every 6 weeks until Week 60, and then every 12 weeks thereafter. Treatment beyond RECIST v1.1– defined disease progression was permitted if the patient was clinically stable and considered to be deriving clinical benefit by the investigator.1
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PFS and ORR were assessed by BICR.1
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Other exploratory endpoints included biomarkers, pharmacokinetics, immunogenicity, and PFS-2.3
The starting dose of CABOMETYX was 40 mg in CheckMate-9ER1
Stratification factors2,6
- IMDC risk group (favorable vs intermediate vs poor)
- PD-L1 tumor expression (≥1% vs <1% or indeterminate)
- Geographic region (United States, Canada, Western and Northern Europe vs rest of world)
IMDC risk distribution in CheckMate-9ER was representative of aRCC population1,2,6-8
Baseline Characteristics WERE Balanced Across Treatment Arms6
No. (%) | |||
CABOMETYX + OPDIVO |
sunitinib |
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Age (years) | |||
<65 | 191 (59.1) | 210 (64.0) | |
≥65 | 132 (40.9) | 118 (36.0) | |
Geographic region | |||
US/Canada/W Europe/N Europe | 158 (48.9) | 161 (49.1) | |
Rest of world | 165 (51.1) | 167 (50.9) | |
Karnofsky performance status | |||
70 | 14 (4.3) | 18 (5.5) | |
80 | 52 (16.1) | 67 (20.4) | |
90 | 110 (34.1) | 112 (34.1) | |
100 | 147 (45.5) | 129 (39.3) | |
Not reported | 0 | 2 (0.6) | |
Baseline IMDC prognostic score2 | |||
Favorable | 74 (22.9) | 72 (22.0) | |
Intermediate | 188 (58.2) | 188 (57.3) | |
Poor | 61 (18.9) | 68 (20.7) | |
Time from diagnosis to randomization6 | |||
<1 year | 210 (65.0) | 214 (65.2) | |
≥1 year | 112 (34.7) | 111 (33.8) | |
Not reported | 1 (0.3) | 3 (0.9) | |
Prior nephrectomy6 | |||
Yes | 222 (68.7) | 233 (71.0) | |
No | 101 (31.3) | 95 (29.0) | |
Prior radiotherapy6 | |||
Yes | 46 (14.2) | 45 (13.7) | |
No | 277 (85.8) | 283 (86.3) | |
PD-L1+ status6 | |||
≥1% | 81 (25.1) | 81 (24.7) | |
<1% or indeterminate | 232 (71.8) | 240 (73.2) | |
Not reported | 10 (3.1) | 7 (2.1) | |
Sarcomatoid features6 | |||
Yes | 34 (10.5) | 41 (12.5) | |
No | 279 (86.4) | 278 (84.8) | |
Not reported | 10 (3.1) | 9 (2.7) | |
Stage at initial diagnosis6 | |||
Stage IV | 167 (51.7) | 173 (52.7) | |
Non-stage IV | 150 (46.4) | 148 (45.1) | |
Not reported | 6 (1.9) | 7 (2.1) | |
No. of metastatic sites3 | |||
1 | 63 (19.5) | 69 (21.0) | |
≥2 | 259 (80.2) | 256 (78.0) | |
Most common sites of metastasis3,6 | |||
Lung | 238 (73.7) | 249 (75.9) | |
Lymph node | 130 (40.2) | 131 (39.9) | |
Liver | 73 (22.6) | 53 (16.2) | |
Bone | 78 (24.1) | 72 (22.0) | |
Adrenal gland | 36 (11.1) | 36 (11.0) |

Primary Analysis: secondary endpoint Overall Survival (OS)1-3
OS outcomes show early and sustained separation of curves in the primary analysis
Primary analysis results: OS
Median follow-up time of 18.1 months; range: 10.6-30.6 months1,3

Extended follow-up analysis results: OS1
Median follow-up time of 32.9 months; range: 25.4-45.4 months8

Primary analysis: primary endpoint Progression-Free Survival (PFS), secondary endpoint Objective Response Rate (ORR)3§
Median PFS and ORR Doubled
Primary analysis results in the ITT population: PFS1
Median follow-up time of 18.1 months; range: 10.6-30.6 months3

Primary analysis results in the ITT population: ORR1
orr was doubled1


At the time of primary analysis, only 5.6% of patients had progressive disease with CABOMETYX + OPDIVO vs 13.7% of patients with sunitinib3||
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PFS and ORR were assessed by BICR.1
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Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of 1 or more new lesions is also considered progression.)3
Extended follow-up analysis results: PFS and ORR1
Median follow-up time of 32.9 months; range: 25.4-45.4 months5
Median PFS5§

ORR5§

12.4% of patients achieved a CR with CABOMETYX + OPDIVO vs 5.2% with sunitinib8
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PFS and ORR were assessed by BICR.1
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NCCN Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
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NCCN Category 2A: based on lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
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NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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The approval of CABOMETYX with OPDIVO in 1L aRCC was based on a randomized (1:1), open-label, Phase 3 trial vs sunitinib in patients with previously untreated aRCC with a clear-cell component.
1L=first-line; 2L=second-line; aRCC=advanced renal cell carcinoma; BICR=blinded independent central review; CI=confidence interval; CR=complete response; HR=hazard ratio; HRQoL=health-related quality of life; IMDC=International Metastatic RCC Database Consortium; IO=immunotherapy; ITT=intent to treat; IV=intravenous; NE=not estimable; NR=not reached; ORR=objective response rate; OS=overall survival; PD-L1=programmed cell death ligand 1; PFS=progression-free survival; PFS-2=progression-free survival after subsequent therapy; PO=by mouth; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; TKI=tyrosine kinase inhibitor.
References:
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2022.
- Motzer RJ, Choueiri TK, Powles T, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma: outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate 9ER. Poster presented at Genitourinary Cancers Symposium; February 11-13, 2021.
- Choueiri TK, Powles T, Burotto M, et al; CheckMate 9ER Investigators. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma [protocol]. N Engl J Med. 2021;384(9):829-841.
- Apolo AB, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma: outcomes by baseline disease characteristics in the phase 3 CheckMate 9ER trial. Poster presented at American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021.
- Powles T, Choueiri TK, Burotto M, et al. Final overall survival analysis and organ-specific target lesion assessments with 2-year follow-up in CheckMate 9ER: nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma. Poster presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium; February 17-19, 2022.
- Data on file. Exelixis, Inc.
- Savard M-F, Wells JC, Graham J, et al. Real-world assessment of clinical outcomes among first-line sunitinib patients with clear cell metastatic renal cell carcinoma (mRCC) by the International mRCC Database Consortium risk group. Oncologist. 2020;25(5):422-430.
- Heng DYC, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor–targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794-5799.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer V.2.2023. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed August 3, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.