Avid Bioservices Inc (CDMO)

[freethemice]

I will give you one example. Avastin + carboplatin+paclitaxel in front-line NSCLC.
The phase 3 trial is the Sandler et al. trial, NEJM, 2006.
http://www.nejm.org/doi/full/10.1056/NEJMoa061884
The phase 2 trial was Johnson et al, 2004, Journal of Clinical Oncology.
http://jco.ascopubs.org/content/22/11/2184.abstract
From the phase 3 NEJM paper:
"A randomized phase 2 study, involving patients
with advanced non–small-cell lung cancer who
had not previously received chemotherapy, compared
paclitaxel and carboplatin alone with paclitaxel
and carboplatin plus bevacizumab, with
bevacizumab at a dose of 7.5 mg or 15 mg per kilogram
of body weight intravenously every 3 weeks.15
In the group receiving the higher dose of bevacizumab,
as compared with the two other groups,
the median time to disease progression was significantly
longer. However, of the 66 patients who
received bevacizumab, life-threatening pulmonary
hemorrhage occurred in 6, including four fatal
events. Serious hemorrhagic events appeared to be
more common among patients with predominantly
squamous-cell carcinomas. These preliminary
results prompted the present phase 3 study, which
was designed to investigate whether the addition
of bevacizumab to paclitaxel and carboplatin improves
survival in patients with metastatic non–squamous-cell, non–small-cell lung cancer."

This is the subgroup analysis for the non-squamous patients in the phase 2 trial.

Note that although the TTP for the 15mg/kg dose group is significant,
for survival neither group is significant.
So this is an example of a phase 2 trial that is not significant for survival,
and yet the phase 3 trial was carried out. There are many examples of this.