CheckMate 025:
A randomized, open-label,
phase III study of nivolumab
versus everolimus in
advanced renal cell
carcinoma
Padmanee Sharma, Bernard Escudier, David F. McDermott, Saby George,
Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman,
Giuseppe Procopio, Elizabeth R. Plimack, Daniel Castellano, Howard Gurney,
Frede Donskov, Petri Bono, John Wagstaff, Thomas C. Gauler, Takeshi Ueda,
Li-An Xu, Ian M. Waxman, Robert J. Motzer,
on behalf of the CheckMate 025 investigators
Introduction
▪ Each year, an estimated 338,000 new cases of renal-cell
carcinoma are diagnosed worldwide, and approximately 30% of
patients present with metastatic disease at the time of diagnosis
▪ A number of targeted therapies have been approved for the
treatment of advanced or metastatic RCC based on PFS
▪ Current therapies provide limited OS benefit in patients who
have been previously treated, highlighting a significant unmet
medical need
▪ This phase III study compared nivolumab, a PD-1 immune
checkpoint inhibitor, versus everolimus in patients with mRCC
after prior systemic therapy
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RCC, renal cell carcinoma; PFS, progression-free survival; OS, overall survival; PD-1, programmed death-1.
Study design and endpoints
Randomized, open-labeled phase III study to compare nivolumab
with everolimus in patients with advanced RCC after prior
systemic therapy (NCT01668784)
Nivolumab
Randomize 1:1
Enrolled patients
• Previously
treated advanced
or metastatic
clear-cell RCC
• 1 or 2 prior antiangiogenic
treatments
(N = 410)
3 mg/kg every 2 weeks
intravenous
Everolimus
(N = 411)
10 mg/day
oral
•
Treat until progression or
intolerable toxicity
•
Treatment beyond
progression was permitted if
drug was tolerated and
clinical benefit was noted
Disease assessments
• Every 8 weeks from randomization through 12 months
• Then every 12 weeks until progression or treatment discontinuation
Primary endpoint
• Overall survival (OS)
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Overall survival
Median OS, months (95% CI)
1.0
Nivolumab (N = 410)
25.0 (21.8–NE)
Everolimus (N = 411)
19.6 (17.6–23.1)
HR (98.5% CI),
0.73 (0.57–0.93)
P = 0.0018
Overall Survival (Probability)
0.9
0.8
0.7
0.6
0.5
Nivolumab
0.4
Everolimus
0.3
0.2
0.1
0.0
0
3
6
9
12
15
18
21
24
27
30
33
Months


The risk of death was reduced by 27% in patients in the nivolumab treatment group compared with
those in the everolimus group
Study stopped after planned interim analysis (398 deaths) because assessment by an independent
data monitoring committee concluded that the study met its primary endpoint, demonstrating
superior OS for nivolumab
This means that patients are more likely to live when treated with nivolumab versus everolimus
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HR, hazard ratio; NE, not estimable.
Objective response rate
P < 0.0001
Objective Response Rate (%)
30
25
25
20
15
10
5
5
0
Nivolumab
Everolimus
 Patients on nivolumab treatment had a significantly better objective
response rate than those on everolimus treatment
This means that more patients responded to treatment with nivolumab than to
treatment with everolimus
5
Treatment-related AEs
 Grade 3 or 4 treatment-related AEs were less frequent with
nivolumab than with everolimus and treatment-related
adverse events leading to discontinuation were experienced
by fewer patients treated with nivolumab
 The most common treatment-related AEs of any grade
reported in the nivolumab arm were fatigue (33%), nausea
(14%), and pruritus (14%), and in the everolimus arm, fatigue
(34%), stomatitis (29%), and anemia (24%)
 There were no treatment-related deaths in the nivolumab
treatment arm
This suggests that nivolumab has a favorable safety profile in
patients with mRCC
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AE, adverse event; mRCC, metastatic renal cell carcinoma.
Key conclusions
▪ CheckMate 025 met its primary endpoint, demonstrating OS superiority
with nivolumab versus everolimus
▪ This is the only phase III trial to demonstrate a survival advantage in
previously-treated patients with mRCC versus standard therapy
▪ Nivolumab was associated with a greater number of objective
responses than everolimus
▪ The survival improvement and favorable safety profile demonstrated in
this phase III trial provides evidence for nivolumab as a potential new
treatment option for previously treated patients with mRCC
▪ Based on the positive results of this trial, nivolumab was granted a
breakthrough therapy designation from the FDA for advanced RCC,
reinforcing the importance of these results in a patient population with
large unmet medical need
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