Avid Bioservices Inc (CDMO)

[freethemice]

Results from the phase IIa first-line NSCLC were reported in June 2011. The PR stated:

promising median overall survival (MOS) of 12.4 months from a Phase II clinical trial evaluating bavituximab plus
carboplatin and paclitaxel in patients with previously untreated, locally-advanced or metastatic non-small cell lung cancer
(NSCLC). This survival is 20% longer than the 10.3 month MOS from a separate historic control trial using carboplatin and
paclitaxel alone in a similar patient population

The historic control trial referred to is this 2006 phase III study by Sandler et al.
of Avastin + C/P vs C/P published in the NEJM:
http://www.nejm.org/doi/full/10.1056/NEJMoa061884
Here are the patient characteristics from that trial


Now here are the patient characteristics from the poster presented at the 2010 ASCO
meeting for the phase IIa bavi + C/P vs. C/P trial.

Note that in almost every common category there are big differences. The percentage with stage IV
disease are fairly close (78% vs 73%). Notice especially the PS 0, 1 scores (40%, 60% vs. 4%, 96%).
The PR went on:

"A two month extension in patient survival is significant in this aggressive form of cancer and we are excited to have another
therapy in later-stage clinical development to meet this urgent medical need," commented Raghunadharao Digumarti, M.D.,
principal investigator of this trial and professor and head of the Department of Medical Oncology at Nizam's Institute of Medical
Sciences, Hyderabad, India. "As a novel monoclonal antibody targeting a novel universal target on all solid tumors, bavituximab
is one of the most promising new therapeutic approaches for patients with lung and other forms of cancer."

So I searched for a first-line NSCLC trial whose control arm would provide a better historic control than
the 2006 Sandler et al Avastin study. I found a phase II trial of talactoferrin + C/P vs. C/P published in 2011.
The lead author is the same Raghunadharao Digumarti. The trial was done entirely in India, as was the bavi trial.
http://journals.lww.com/jto/Fulltext/2011/06000/A_Randomized,_Double_Blind,_Placebo_Controlled,.18.aspx
Here are the patient characteristics from the trial:

Note how much closer these are to the bavi trial than the Avastin trial. The number of patients is also
similar (55 vs 49). The PS 0, 1 scores are almost identical. I would say this is a much better control arm
to compare with the bavi + C/P arm than the control arm from the Avastin study.

There is another issue not listed in the above tables. In the bavi + C/P trial a lower dose of carboplatin (AUC=5)
and paclitaxel (175 mg/m^2) was used than is normally used here in the US. In the talactoferrin (TLF) trial they used the
exact same dosage. The Avastin trial used a higher dosage, carboplatin (AUC=6) and paclitaxel (200 mg/m^2).
There is this comment about this in the text:

The rationale for choosing doses of C/P slightly lower than doses most commonly used in North America was the
lack of prior experience with the combination of TLF and C/P and because these doses of C/P are commonly used
in some parts of the world and community practices in the United States.

The study results are then:
bavituximab+C/P: ORR = 43%; PFS = 6.1 months; MOS = 12.4 months
TLF control C/P: ORR = 27%; PFS = 4.2 months; MOS = 8.5 months
That 3.9 month increase is a 46% increase in MOS.