flipper44 Member Level Wednesday, 12/08/21 01:34:23 PM
Re: norisknorewards post# 424753 0.110
Post # of 424835
The significance? Briefly, the ECA primary endpoints in the DCVax-l trial, particularly for newly diagnosed GBM, rely upon the historical observations that GBM (especially as now defined) has, on average, a very predictable (dismal) survival curve when standard of care is used.
The subset in the BMY trial — checkmate 548 — was of concern to some because it seemed at first blush to buck the predictable nature of newly diagnosed GBM (albeit just the MGMT methylated subset) survival when treated with standard of care, because the SOC arm was not consistent with other large GBM trials’ SOC arms.
My contention was the checkmate 548 trial results and failure had out of ordinary SOC results because they likely had different demographics — such as IDH-1 mutation, and since around 2015, it’s been known idh-1 mutation + methylated mgmt doubles survival compared to methylated MGMT alone. The Checkmate 548 trial did not start until 2016. (Checkmate 548 did not really breakdown any important demographics yet)
Lykiri’s brilliant move was to contact the Co-author and determine if this might have occurred. The co-author wrote back that he could not discern this because the sponsor of checkmate 548 was not interested in determining the idh mutation prevalence in either arm of their trial, because the trial was a failure for their sponsor’s product.
The significance is that the Checkmate 548 trial’s data is unreliable for future comparisons because it includes data that no longer can be considered GBM, and there is no way to decipher which data points that would be.
The long and short of it is that Checkmate 548 does not effect or play a part in the otherwise reliable historical trend that can allow an ECA comparison of SOC with DCVax-l’s treatment arm.
