Hartland,

Please read my previous post from June. It explains the 3 + 3 design very clearly. If indeed Zenith is following the traditional 3 + 3 design, which I think they indicated in their Q2 update, then the following are the rules. From this article that I cited in my previous post:

" If none of the three patients in a cohort experiences a dose-limiting toxicity, another three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a dose-limiting toxicity, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience dose-limiting toxicities (ie, ≥33% of patients with a dose-limiting toxicity at that dose level). The recommended dose for phase II trials is conventionally defined as the dose level just below this toxic dose level."

So you asked "Would I be correct that if toxicity had been a factor in cycle one they would have stopped likewise in 2and 3?" If they had a dose-limiting toxicity (DLT) with the first dose, then ZEN-3694 would likely not be a viable clinical candidate anymore. Let's say they had 3 patients in the first cycle and 1 of the 3 had a DLT. Then for cycle 2, they would have to add 3 more patients but stay at the same original dose. If 2 patients of the 6 have DLTs at this dose, then this dose is considered the maximally tolerated dose. So if they reach the maximally tolerated dose at dose 1 or dose 2, then this is likely not a safe compound for future clinical use.

This is my understanding of the trial design, which may be wrong. I'm optimistic (of course) that this will be a safe and effective compound. Let's hope that no DLTs have been encountered yet and that the efficacy will be off the charts!

BearDownAZ