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CheckMate 548

Chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter (CheckMate 548)

Phase 3N = 716NCT02667587

Population
Patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter; 716 randomised
Design
Randomised phase 3 trial (1:1) of nivolumab (240 mg every 2 weeks for 8 doses, then 480 mg every 4 weeks) or placebo plus radiotherapy (60 Gy over 6 weeks) and temozolomide (75 mg/m2 daily during radiotherapy, then 150-200 mg/m2 on days 1-5 of every 28-day cycle for 6 cycles); primary endpoints progression-free survival and overall survival in patients without baseline corticosteroids and in all randomised patients
Primary endpoint
PFS, OS
Arms
  • Nivolumab plus radiotherapy-temozolomide (experimental): Nivolumab with radiotherapy 60 Gy and temozolomide
  • Placebo plus radiotherapy-temozolomide (control): Placebo with radiotherapy 60 Gy and temozolomide
People
Lim M
PFSHR 1.1 (95% CI 0.9–1.3)Δ median PFS+0.3 monthsOSHR 1.1 (95% CI 0.9–1.3)Δ median OS−3.2 monthsOSHR 1.1 (95% CI 0.9–1.4)Δ median OS−1.7 months
Show the numbers
Results reported for CheckMate 548
EndpointAnalysisNivolumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomideEffect
PFSRandomised patients (n=716); the abstract does not label the population for these figuresProgression-free survival by blinded independent central reviewprimaryLim 2022median 10.6 months (8.9–11.8)median 10.3 months (9.7–12.5)HR 1.1 (95% CI 0.9–1.3)Data cutoff 22 December 2020.
OSRandomised patients (n=716); the abstract does not label the population for these figuresOverall survivalprimaryLim 2022median 28.9 months (24.4–31.6)median 32.1 months (29.4–33.8)HR 1.1 (95% CI 0.9–1.3)The abstract states nivolumab added to radiotherapy plus temozolomide did not improve survival.
OSPatients without baseline corticosteroidsOverall survival in patients without baseline corticosteroids (co-primary population)primaryLim 2022median 31.3 months (28.6–34.8)median 33 months (31.0–35.1)HR 1.1 (95% CI 0.9–1.4)
Results reported for CheckMate 548
EndpointAnalysisNivolumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomideEffect
PFSRandomised patients (n=716); the abstract does not label the population for these figuresProgression-free survival by blinded independent central reviewprimaryLim 2022median 10.6 months (8.9–11.8)median 10.3 months (9.7–12.5)HR 1.1 (95% CI 0.9–1.3)Data cutoff 22 December 2020.
OSRandomised patients (n=716); the abstract does not label the population for these figuresOverall survivalprimaryLim 2022median 28.9 months (24.4–31.6)median 32.1 months (29.4–33.8)HR 1.1 (95% CI 0.9–1.3)The abstract states nivolumab added to radiotherapy plus temozolomide did not improve survival.
OSPatients without baseline corticosteroidsOverall survival in patients without baseline corticosteroids (co-primary population)primaryLim 2022median 31.3 months (28.6–34.8)median 33 months (31.0–35.1)HR 1.1 (95% CI 0.9–1.4)
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS1.10.9–1.3
OS1.10.9–1.3
OS1.10.9–1.4
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Nivolumab plus radiotherapy-temozolomide (experimental)
  • Placebo plus radiotherapy-temozolomide (control)

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

Data table (modelled values)
MonthsNivolumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomide
0100.0%100.0%
763.3%62.4%
1342.7%41.7%
2027.0%26.0%
2717.1%16.3%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%020406080Months (modelled)
  • Nivolumab plus radiotherapy-temozolomide (experimental)
  • Placebo plus radiotherapy-temozolomide (control)

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

Data table (modelled values)
MonthsNivolumab plus radiotherapy-temozolomidePlacebo plus radiotherapy-temozolomide
0100.0%100.0%
2061.9%64.9%
4038.3%42.2%
6023.7%27.4%
8014.7%17.8%
Primary publication: Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022;24(11):1935-1949. PubMedDOI

Appears in

Sources

  1. Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022;24(11):1935-1949.

    PubMedDOI