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 endpoints3‡ HRQoL |
The starting dose of CABOMETYX was 40 mg in CheckMate-9ER1
- Excluded patients with autoimmune disease or other medical conditions requiring systemic immunosuppression1
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Median follow-up was 18.1 months, with an extended median follow-up of 23.5 months (range: 16.0-36.0 months)2,3
Stratification factors2,5
- IMDC risk group (favorable vs intermediate vs poor)
- PD-L1 tumor expression (≥1% vs <1% or indeterminate)
- Geographic region (US, Canada, Western and Northern Europe vs rest of world)
- *
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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
IMDC risk distribution in CheckMate-9ER representative of aRCC population1,2,5-7
Baseline Characteristics Balanced Across Treatment Arms5
No. (%) | |||
CABOMETYX + OPDIVO |
sunitinib |
||
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 randomization5 | |||
<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 nephrectomy5 | |||
Yes | 222 (68.7) | 233 (71.0) | |
No | 101 (31.3) | 95 (29.0) | |
Prior radiotherapy5 | |||
Yes | 46 (14.2) | 45 (13.7) | |
No | 277 (85.8) | 283 (86.3) | |
PD-L1+ status5 | |||
≥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 features5 | |||
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 diagnosis5 | |||
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) | |
Most common sites of metastasis3,5 | |||
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
Primary analysis results: OS
Median follow-up time of 18.1 months; range: 10.6-30.6 months1,3

- Median OS not reached in either treatment arm1
Extended follow-up analysis results: OS
Median follow-up time of 23.5 months; range: 16.0-36.0 months2

- Median OS not reached in the CABOMETYX + OPDIVO arm2
Primary analysis: primary endpoint Progression-Free Survival (PFS), secondary endpoint Overall Response Rate (ORR)3§
Median PFS and ORR Doubled
Primary analysis results: PFS and ORR
Median follow-up time of 18.1 months; range: 10.6-30.6 months3
median pfs was doubled1

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||
Extended follow-up analysis results: PFS and ORR
Median follow-up time of 23.5 months; range: 16.0-36.0 months2
median pfs2

ORR2


- §
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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
NCCN Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. NCCN=National Comprehensive Cancer Network® (NCCN®). 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.
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; ITT=intent to treat; IV=intravenous; NE=not estimable; 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.
References:
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2021.
- 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.
- 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.4.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved.Accessed December 21, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.