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Bending the Curve Trial by Trial
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ACT IV

Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV)

Phase 3N = 745NCT01480479

Population
Adults with newly diagnosed, centrally confirmed EGFRvIII-expressing glioblastoma who had undergone maximal resection and completed chemoradiation without progression; 745 enrolled and randomised (371 rindopepimut, 374 control), of whom 405 had minimal residual disease and 338 significant residual disease
Design
Randomised, double-blind, international phase 3 trial (165 hospitals in 22 countries); 1:1 randomisation to rindopepimut (500 μg with 150 μg GM-CSF) or control (100 μg keyhole limpet haemocyanin) by monthly intradermal injection until progression or intolerance, concurrent with temozolomide 150-200 mg/m2 for 5 of 28 days for 6-12 cycles or longer; primary endpoint overall survival in patients with minimal residual disease (enhancing tumour under 2 cm2 after chemoradiation by central review), modified intention to treat; terminated for futility after a preplanned interim analysis
Primary endpoint
OS
Arms
  • Rindopepimut plus temozolomide (experimental, n = 371): Rindopepimut 500 μg admixed with GM-CSF 150 μg monthly intradermally plus temozolomide
  • Control (keyhole limpet haemocyanin) plus temozolomide (control, n = 374): Control injection of keyhole limpet haemocyanin 100 μg monthly intradermally plus temozolomide
People
Weller M, ACT IV trial investigators
OSHR 1.01 (95% CI 0.79–1.30)Δ median OS+0.1 months
Show the numbers
Results reported for ACT IV
EndpointAnalysisRindopepimut plus temozolomideControl (keyhole limpet haemocyanin) plus temozolomideEffect
OSPatients with minimal residual disease (modified intention to treat)Overall survival in patients with minimal residual disease (primary endpoint)finalWeller 2017median 20.1 months (18.5–22.1)median 20 months (18.1–21.9)HR 1.01 (95% CI 0.79–1.30)P=0.93The study was terminated for futility after a preplanned interim analysis; this is the final analysis.
Results reported for ACT IV
EndpointAnalysisRindopepimut plus temozolomideControl (keyhole limpet haemocyanin) plus temozolomideEffect
OSPatients with minimal residual disease (modified intention to treat)Overall survival in patients with minimal residual disease (primary endpoint)finalWeller 2017median 20.1 months (18.5–22.1)median 20 months (18.1–21.9)HR 1.01 (95% CI 0.79–1.30)P=0.93The study was terminated for futility after a preplanned interim analysis; this is the final analysis.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS1.010.79–1.3
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%01020304050Months (modelled)
  • Rindopepimut plus temozolomide (experimental)
  • Control (keyhole limpet haemocyanin) plus temozolomide (control)

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

Data table (modelled values)
MonthsRindopepimut plus temozolomideControl (keyhole limpet haemocyanin) plus temozolomide
0100.0%100.0%
1363.9%63.7%
2542.2%42.0%
3827.0%26.8%
5017.8%17.7%
Primary publication: Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373-1385. PubMedDOI

Appears in

Sources

  1. Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373-1385.

    PubMedDOI