OnCo
trialsTrialNegative

ACT IV

A double-blind test of a promising glioblastoma vaccine that showed no benefit, and taught the field how misleading historical-control comparisons can be.

745 randomised. Median OS 20.1 vs 20.0 months in the minimal-residual-disease population. Both arms outperformed historical expectations, and EGFRvIII was lost at recurrence in most patients irrespective of arm. Lancet Oncology 2017.

Setting
Newly diagnosed EGFRvIII+ glioblastoma with minimal residual disease: rindopepimut + temozolomide vs control (KLH) + temozolomide
Phase
Phase 3
Sponsor
Celldex Therapeutics
Registry
Headline result
OS 20.1 vs 20.0 months; no benefit.
Reported
2016
Enrolled
745
Replication
Failed to replicate the phase 2 ACT III signal; EGFRvIII loss at recurrence in both arms undermined the target.

Outcomes

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In plain words
What these results mean for people, not percentages
745 people took part
Overall survival, minimal residual disease populationprimarysurvival endpoint
  • Median 20.1 vs 20 months with Rindopepimut + temozolomide compared with Control + temozolomide; about 0.1 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Put another way, the treated group had about 1 percent higher chance of the event at any given time (hazard ratio 1.01, likely range 0.79 to 1.3).
  • The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
  • These results apply to the people the trial enrolled: Newly diagnosed EGFRvIII+ glioblastoma with minimal residual disease: rindopepimut + temozolomide vs control (KLH) + temozolomide. People in a different situation may not see the same effect.
  • The trial selected people by a biomarker (EGFRvIII); the result should not be assumed for people whose cancer does not have it.
  • Not significant.

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 participants enrolled.

Overall survival, minimal residual disease populationprimary
HR 1.01 (0.79–1.3)
Rindopepimut + temozolomide
20.1 mo
Control + temozolomide
20 mo

Not significant

Source
EndpointArmnValueHR (95% CI)pSource
Overall survival, minimal residual disease populationprimaryRindopepimut + temozolomide37120.1 months1.01 (0.79–1.3)link
Control + temozolomide37420 months
Replication
Failed to replicate the phase 2 ACT III signal; EGFRvIII loss at recurrence in both arms undermined the target.

Connected

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