Spectrum Pharmaceutecals Inc (SPPI)

[antihama]

Why was Pozi Z20 C2 successful whereas C1 wasn’t? I was totally surprised by the results. I did say in the past it had a punchers chance of success but expected it to fail, but man, that punch landed.

Well, first of all they were testing Her 2 ex 20mu patients and not EGFR. Dr Heymach, at the 18th WCLC in Oct 2017, when asked by Ed White, if he expected to see different results for the MDACC Her2 cohort stated (paraphrasing) ”the Her2 (location ) is shifted to the left (compared to EGFR) so location of HER2 insertions are in a more sensitive region so I would predict they would be sensitive based on what I shown today” and that would explain why they did better than egfr” but in the MDACC trial, w only ~10 patients worth of data, egfr and Her2 were basically equivalent. So, from that view, I would have expected similar results to MDACC C1/2 but maybe there were too few patients to get accurate statistics previously for C2 and the different region further to the left of the loop played a role.

By the time Z20 C1 results came out, C2 was fully enrolled so lessons learned from dose interruption and dose modification weren’t incorporated for C2. What I did find interesting was FL saying Monday “But clearly, the experience of the investigator is always important and they know how to use the drug better, how to handle AEs”. He also mentions that some trial sites had 10 or 15 patients while others had 1 or 2. That makes me think that was the reason why the MDACC trial was so successful which was the investigators were all at the same site and were seeing many patients w the same issues and learned how to keep them on trial. The investigators for the Z20 cohort 1 trial were all new to dealing w the patients and pozi (except for the MDACC trial site) and there was a learning curve from which the Z20 cohort 1 couldn’t overcome. Cohort 2 used most of the same trial sites and the investigators were learning to deal w pozi and the patients and as a result had a successful outcome.

ESMO late breaking abstracts deadline is August 17th so hopefully they'll have an abstract for Cohort 2 at ESMO.

C2 was fully enrolled 5/28/19 by the time protocol amendments were issued and didn't help C2 but for C3 that was fully enrolled by 5/7/20, nearly a year later, the protocol amendments probably did help some, and probably more importantly, had by now experienced investigators at the trial sites. This bodes well for cohort 3.