Replies to post #75495 on Avid Bioservices Inc (CDMO)

[Chocolate Moose]

I found this interesting from our associate Dr Weiss on nsclc and tki inhibitors. Sorry if its old news.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030820


some snippets

While effective treatments for KRAS-driven tumors have generally been lacking, significant progress has been made in the development of tyrosine kinase inhibitors (TKI) that selectively block the activity of constitutively activated RTKs [4]. Perhaps the best example of this therapeutic strategy is the development of small-molecule inhibitors of EGFR, including gefitinib and erlotinib [5], [6]. Patients with specific activating mutations to EGFR respond favorably to these drugs, though most eventually relapse or progress due to a variety of acquired resistance mechanisms [7].

Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations.

Our data demonstrate that STAT3 activity is unaffected by TKI treatment in several different cellular contexts.

Targeted Kinase Inhibitors Fail to Downregulate STAT3 Phosphorylation

[Thurly]

From the time PPHM announced full enrollment of the first-line NSCLC trial on September 8, 2011 to the time they announced ORR on December 29, 2011 was 16 weeks exactly - Thursday to Thursday.

We're now in middle of the the 18th week since Peregrine announced full enrollment of the second-line trial on October 6, 2011.

Peregrine always said 2H for the data release on the 2nd line trial. But they would clearly have the ORR data available in Q1. Why the delay in the data release?

I think PPHM announces ORR at ASCO, which means no announcement until they present June 1-5, 2012.

Abstract Submission Deadline February 1, 2012
ASCO late breaker application date: April 2, 2012
Abstracts released online: May 16, 2012

My WAG and definitely FWIW.