Replies to post #99388 on NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

Surgery is an integral part of DCVax-Lysate treatment and so that is why they include the period of time from surgery to Baseline in their conclusion of 14.7 months from first recurrent surgery, when comparing against a treatment option that did not necessarily include surgery, like Avastin. That was the purpose of that abstract to compare one treatment survival time against another and one includes surgery and so TTT needed to be part of the analysis to have the same start point.

But surgery to Baseline is not included in the time when they are measuring EFFICACY to the vaccine alone -- in term of thinking how long it delays progression or death in patients. In order for DCVax-L to be approved it needs to be evaluated on its own merits, as an adjuvant treatment. Surgery, otherwise known as extent of resection (EOR), is only analyzed a covariate. Those prior Phase I and I/II did not power to analyze EOR. Surgery is already approved as standard of care and that isn't going away anytime soon. DCVax-L efficacy was and is measure against standard of care. Standard of care includes Surgery + Radiation + TMZ in both arms. And so you're thinking about it incorrectly. While surgery to get the lysate is importand, that is an event that is included in STUPP protocol measurement. Efficacy for the vaccine is measured from Baseline, same as the current Phase III. And the time from surgery to Baseline is left out of the primary and secondary analysis as against is standard to both arms. If they REPORT back to surgery or newly diagnosed point then that TTT (from surgery to Baseline) and TTT for placebo crossover (from newly diagnosed all the way to recurrent/progression Baseline) would need to be added back. As for this Phase III, Surgery will likely be included in the tertiary analysis when they look at TTP in those patients, as they need to compare to historical controls, when concurrent standard of care treatments start.

Phase III protocol:

In the Phase III trial, PFS and survival times will be calculated from time of randomization, which is expected to occur approximately three months after initial
surgery.

And:

3.1. OBJECTIVES
3.1.1. Primary objective
The primary objective of this study is to compare progression free survival (PFS) between patients in the DCVax-L cohort and patients in the placebo cohort in patients with no evidence of disease progression at BASELINE.

3.1.2. Secondary objective
The secondary objective of this study is to compare Overall Survival (OS) between patients in the DCVax-L group and patients in the placebo group in patients with no evidence of disease progression at BASELINE.