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ACT IV was a double-blind phase 3 test of rindopepimut, a vaccine against the EGFRvIII mutant protein, in 745 patients with newly diagnosed glioblastoma. It showed no benefit over a control vaccine, and because both arms beat historical expectations it taught the field how misleading historical-control comparisons can be.
ACT IV, trial NCT01480479 sponsored by Celldex Therapeutics and reported in 2016, was a double-blind test of the EGFRvIII vaccine rindopepimut in newly diagnosed glioblastoma with minimal residual disease that showed no benefit, and it taught the field how misleading historical-control comparisons can be. It randomised 745 patients to rindopepimut or a control vaccine with temozolomide and found no difference in overall survival, while both arms outperformed historical expectations and EGFRvIII was lost at recurrence in most patients whichever arm they were in. OnCo links it to EGFR as a target, the EGFRvIII term, rindopepimut and the brain as a bottleneck, and the trial failed to replicate the phase 2 ACT III signal. Whether a single-antigen vaccine can ever work against a target the tumour so readily discards is the question its failure answered in the negative.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
745 enrolled.
Not significant
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, minimal residual disease populationprimary | Rindopepimut + temozolomide | 371 | 20.1 months | 1.01 (0.79 to 1.3) | - | link |
| Control + temozolomide | 374 | 20 months |
Shares Blinding (double-blind, open-label, placebo-controlled), Control arm and comparator (investigator's choice), Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Blinding (double-blind, open-label, placebo-controlled), Control arm and comparator (investigator's choice), Placebo.
Shares Blinding (double-blind, open-label, placebo-controlled), Placebo.
Shares External and synthetic control arms, Control arm and comparator (investigator's choice), Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover.
Shares Blinding (double-blind, open-label, placebo-controlled), Placebo.
Shares EGFRvIII, The brain: barrier and sanctuary, EGFR, Glioma & glioblastoma.
Shares Blinding (double-blind, open-label, placebo-controlled), Placebo.
Shares Off-the-shelf cancer vaccines, Glioma & glioblastoma.