Replies to post #57600 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Well yes but.. the crossover was mandated due to an invasive procedure for the placebo and active treatments. The need to retain patients for assessment of secondary endpoints (with a change to OS co-primary in mind perhaps from the .03 alpha spend reserved) necessitated the cross-over as well.

It was mandated when the trial was designed as a non regisrational P2, unclear if the FDA would have had the same view of a P3.

No need to retain patients for OS, that is eaily followed.

This treatment may be showing efficacy signals on multiple levels. It may show stand alone efficacy with mesenchymal GBM genotype with regard to PFS and OS, stand alone efficacy in mesenchymal phenotype at crossover in OS and potentiation/repotentiation of checkpoint inhibitors and various chemo/radiation therapies with PFS and OS. With this kind of activity possibly going on, FDA will want to figure this all out especially with the biomarker correlations to survival in hand. The data from this trial is just too valuable given that patients are living longer than a 24 month median. Living longer is the gold standard right?

If by "stand alone" you mean comparing a single arm to historical norms, that is an invalid concept. The FDA absolutely does not accept it. And subgroups (unless as an alpha assigned endpoint) are also near useless for registration. Saying the subgroup is predfined means nothing.

The "gold standard" is OS between arm of the ITT population.