CheckMate 025: trial | Bending the Curve: Trial by Trial

CheckMate 025

Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

Phase 3N = 821NCT01668784

Population

Adults with advanced clear-cell renal cell carcinoma previously treated with one or two antiangiogenic regimens

Design

Randomised (1:1), open-label phase 3 trial of nivolumab versus everolimus in patients with advanced clear-cell renal cell carcinoma who had received one or two previous antiangiogenic regimens. The primary end point was overall survival; objective response rate and safety were secondary end points. The primary report is a prespecified interim analysis, conducted after 398 of the 569 deaths required for the final analysis (author manuscript).

Primary endpoint

Arms

Nivolumab (experimental, n = 410): Nivolumab 3 mg per kilogram intravenously every 2 weeks
Everolimus (control, n = 411): Everolimus 10 mg orally once daily

People

Motzer RJ, CheckMate 025 Investigators

OSHR 0.73Δ median OS+5.4 monthsΔ ORR+20 pointsPFSHR 0.88 (95% CI 0.75–1.03)Δ median PFS+0.2 monthsOSHR 0.73 (95% CI 0.62–0.85)

Show the numbers

Results reported for CheckMate 025
Endpoint	Analysis	Nivolumab	Everolimus	Effect
OSAll randomised patients (821)	primaryMotzer 2015	median 25 months	median 19.6 months (17.6–23.1)	HR 0.73P=0.002Hazard ratio for death with a 98.5% confidence interval of 0.57 to 0.93; the 95% CI of the nivolumab median was 21.8 to not estimable. Met the prespecified criterion for superiority (P at or below 0.0148).
ORRAll randomised patients (821)	primaryMotzer 2015	25%	5%	P<0.001Odds ratio 5.98 (95% CI 3.68 to 9.72). Secondary end point.
PFSAll randomised patients (821)	primaryMotzer 2015	median 4.6 months (3.7–5.4)	median 4.4 months (3.7–5.5)	HR 0.88 (95% CI 0.75–1.03)P=0.11Not significantly different.
OSRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	median 25.8 months (22.2–29.8); 26% at 5 y	median 19.7 months (17.6–22.1); 18% at 5 y	HR 0.73 (95% CI 0.62–0.85)Minimum follow-up 64 months.
PFSRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	—	—	HR 0.84 (95% CI 0.72–0.99)P=0.0331
ORRRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	23%	4%	P<0.001

Results reported for CheckMate 025
Endpoint	Analysis	Nivolumab	Everolimus	Effect
OSAll randomised patients (821)	primaryMotzer 2015	median 25 months	median 19.6 months (17.6–23.1)	HR 0.73P=0.002Hazard ratio for death with a 98.5% confidence interval of 0.57 to 0.93; the 95% CI of the nivolumab median was 21.8 to not estimable. Met the prespecified criterion for superiority (P at or below 0.0148).
ORRAll randomised patients (821)	primaryMotzer 2015	25%	5%	P<0.001Odds ratio 5.98 (95% CI 3.68 to 9.72). Secondary end point.
PFSAll randomised patients (821)	primaryMotzer 2015	median 4.6 months (3.7–5.4)	median 4.4 months (3.7–5.5)	HR 0.88 (95% CI 0.75–1.03)P=0.11Not significantly different.
OSRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	median 25.8 months (22.2–29.8); 26% at 5 y	median 19.7 months (17.6–22.1); 18% at 5 y	HR 0.73 (95% CI 0.62–0.85)Minimum follow-up 64 months.
PFSRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	—	—	HR 0.84 (95% CI 0.72–0.99)P=0.0331
ORRRandomised patients (821; 410 nivolumab, 411 everolimus)	long term-updatemedian follow-up 72 monthsMotzer 2020	23%	4%	P<0.001

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.88	0.75–1.03
OS	0.73	0.62–0.85
PFS	0.84	0.72–0.99

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Nivolumab (experimental)
Everolimus (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Nivolumab	Everolimus
0	100.0%	100.0%
16	64.2%	56.8%
31	42.3%	33.4%
47	27.2%	19.0%
63	17.4%	10.8%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Nivolumab (experimental)
Everolimus (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Nivolumab	Everolimus
0	100.0%	100.0%
3	63.6%	62.3%
6	40.5%	38.9%
9	25.8%	24.2%
12	16.4%	15.1%

Appears in

2015 CheckMate 025: nivolumab versus everolimus in treated RCC (2015)

Sources

Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803-13.
PubMed DOI
Motzer RJ, Escudier B, George S, Hammers HJ, Srinivas S, Tykodi SS, et al. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer. 2020;126(18):4156-4167.
PubMed DOI