CheckMate 9ER: trial | Bending the Curve: Trial by Trial

CheckMate 9ER

A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma

Phase 3N = 651NCT03141177

Population

Adults with previously untreated advanced clear-cell renal cell carcinoma

Design

Randomised (1:1), open-label phase 3 trial in previously untreated advanced clear-cell renal cell carcinoma, stratified by IMDC risk score, tumour PD-L1 expression and geographic region. The primary end point was progression-free survival by blinded independent central review; secondary end points included overall survival, objective response by independent review and safety. The paper reports 651 randomised patients (full text).

Primary endpoint

PFS

Arms

Nivolumab plus cabozantinib (experimental, n = 323): Nivolumab 240 mg intravenously every 2 weeks plus cabozantinib 40 mg orally once daily
Sunitinib (control, n = 328): Sunitinib 50 mg orally once daily for 4 weeks of each 6-week cycle

People

Choueiri TK, CheckMate 9ER Investigators

PFSHR 0.51 (95% CI 0.41–0.64)Δ median PFS+8.3 monthsOSHR 0.6Δ 12-month OS+10.1 pointsΔ ORR+28.6 pointsOSHR 0.70 (95% CI 0.55–0.90)

Show the numbers

Results reported for CheckMate 9ER
Endpoint	Analysis	Nivolumab plus cabozantinib	Sunitinib	Effect
PFS	primarymedian follow-up 18.1 monthsChoueiri 2021	median 16.6 months (12.5–24.9)	median 8.3 months (7.0–9.7)	HR 0.51 (95% CI 0.41–0.64)P<0.001Median follow-up 18.1 months is the follow-up for overall survival. Blinded independent central review.
OS	interimmedian follow-up 18.1 monthsChoueiri 2021	85.7% at 12 mo (81.3–89.1%)	75.6% at 12 mo (70.5–80.0%)	HR 0.6P=0.001Hazard ratio for death with a 98.89% confidence interval of 0.40 to 0.89. Median overall survival was not reached in either group (full text).
ORR	primarymedian follow-up 18.1 monthsChoueiri 2021	55.7% (50.1–61.2%)	27.1% (22.4–32.3%)	P<0.001Complete response in 8.0% (nivolumab plus cabozantinib) and 4.6% (sunitinib).
OS	finalmedian follow-up 32.9 monthsMotzer 2022	median 37.7 months	median 34.3 months	HR 0.70 (95% CI 0.55–0.90)P=0.0043Preplanned final overall survival analysis, data cutoff 24 June 2021. The 95% CIs of the medians were 35.5 to not estimable and 29.0 to not estimable.
PFS	long term-updatemedian follow-up 32.9 monthsMotzer 2022	median 16.6 months (12.8–19.8)	median 8.3 months (7.0–9.7)	HR 0.56 (95% CI 0.46–0.68)P<0.0001Updated progression-free survival, data cutoff 24 June 2021.

Results reported for CheckMate 9ER
Endpoint	Analysis	Nivolumab plus cabozantinib	Sunitinib	Effect
PFS	primarymedian follow-up 18.1 monthsChoueiri 2021	median 16.6 months (12.5–24.9)	median 8.3 months (7.0–9.7)	HR 0.51 (95% CI 0.41–0.64)P<0.001Median follow-up 18.1 months is the follow-up for overall survival. Blinded independent central review.
OS	interimmedian follow-up 18.1 monthsChoueiri 2021	85.7% at 12 mo (81.3–89.1%)	75.6% at 12 mo (70.5–80.0%)	HR 0.6P=0.001Hazard ratio for death with a 98.89% confidence interval of 0.40 to 0.89. Median overall survival was not reached in either group (full text).
ORR	primarymedian follow-up 18.1 monthsChoueiri 2021	55.7% (50.1–61.2%)	27.1% (22.4–32.3%)	P<0.001Complete response in 8.0% (nivolumab plus cabozantinib) and 4.6% (sunitinib).
OS	finalmedian follow-up 32.9 monthsMotzer 2022	median 37.7 months	median 34.3 months	HR 0.70 (95% CI 0.55–0.90)P=0.0043Preplanned final overall survival analysis, data cutoff 24 June 2021. The 95% CIs of the medians were 35.5 to not estimable and 29.0 to not estimable.
PFS	long term-updatemedian follow-up 32.9 monthsMotzer 2022	median 16.6 months (12.8–19.8)	median 8.3 months (7.0–9.7)	HR 0.56 (95% CI 0.46–0.68)P<0.0001Updated progression-free survival, data cutoff 24 June 2021.

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

Data table

Endpoint	HR	95% CI
PFS	0.51	0.41–0.64
OS	0.7	0.55–0.9
PFS	0.56	0.46–0.68

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

Show curves

Nivolumab plus cabozantinib (experimental)
Sunitinib (control)

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

Data table (modelled values)

Months	Nivolumab plus cabozantinib	Sunitinib
0	100.0%	100.0%
10	65.9%	43.4%
21	41.6%	17.3%
31	27.4%	7.5%
42	17.3%	3.0%

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

Show curves

Nivolumab plus cabozantinib (experimental)
Sunitinib (control)

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

Data table (modelled values)

Months	Nivolumab plus cabozantinib	Sunitinib
0	100.0%	100.0%
24	64.3%	61.6%
47	42.1%	38.7%
71	27.1%	23.8%
94	17.8%	15.0%

Appears in

2021 CheckMate 9ER: nivolumab plus cabozantinib versus sunitinib (2021)

Sources

Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021;384(9):829-841.
PubMed DOI
Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, et al. 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;23(7):888-898.
PubMed DOI