rkrw, in light of recent research which indicates that pts develop resistance to crizotinib within a year, I'm wondering what type of AP113 P1 trial makes the most sense to you?
Here's what really caught my attention:
"We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene. Cells resistant to higher doses (1 µM) also developed a gatekeeper mutation, L1196M, within the kinase domain, ]rendering EML4-ALK insensitive to crizotinib
Fortunately, "this gatekeeper mutation was readily detected using a unique and highly sensitive allele-specific PCR assay."
I wonder how this will impact the AP113 trial design? It seems like the least risky approach would be to initially go for 2nd line and enroll only pts with the gatekeeper mutation.
