NorthWest Biotherapeutics Inc (NWBO)

[f3tt3f]

FDA has long emphasized OS as the gold standard endpoint in the front-line setting for just about all cancer indications.

Yes, but that's not the end of the discussion.
From the FDA:

Guidance for Industry
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics


www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf


3. Time to Progression and Progression-Free Survival
TTP and PFS have served as primary endpoints for drug approval. TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths. PFS is defined as the time from randomization until objective tumor progression or death. The precise definition of tumor progression is important and should be carefully detailed in the protocol.
a. TTP vs. PFS
Compared with TTP, PFS is the preferred regulatory endpoint. PFS includes deaths and thus can be a better correlate to overall survival. In TTP analysis, deaths are censored, either at the time of death or at an earlier visit representing informative censoring (nonrandom pattern of loss from the study). PFS assumes patient deaths are randomly related to tumor progression. However, in situations where the majority of deaths are unrelated to cancer, TTP can be an acceptable endpoint.

They go on to state some of the issues one might come up against using these as endpoints, but don't (and haven't) ruled them out. - Would OS be a more robust endpoint for DCVax-L?
No. Because of crossover. Is that ideal? No. But there is clearly interest on the FDA's part to usher through promising treatments and therapies. They just need to work out if DCVax-L is one of those.


I'm interested in understanding how Linda Liau is mistaken.