Applying hypotheticals to draw different conclusions smells a tad fishy to me (pardon the pun). I can see why you would be wanting to consider the hypotheticals. The reality is, though, that the benchmarks and the data, as applied and anaylsed by the expert scientists, has been deemed by Prof Miles Prince as worthy of a Ph2 study. As a world-renowned hematologist, I think we can take Prof MP's assessment as authentic in context of the data as presented.
Safety is the primary key objective in the results of Phase 1 trials and efficacy is secondary. The trial design for Ph1 is probably based on reduced drug concentrates across more frequent doses to mitigate unfavourable immune responses in patients who are fragile and close to death. The TCL patients in our trial have advanced malignancies who have failed several prior treatments, so they are sickest of the sick.
Four cycles of treatment involving 5 consecutive days of therapy is demanding. Its interesting to note that out of the 8 patients that dropped out of the trial, 7 had PTCL. That suggests to me that PTCL patients likely have a more debilitating disease than those with CTCL and perhaps lose the mental battle needed to stay positive to persist in the face of a demanding trial regime.
If PTCL patients were to be treated at an earlier stage of their disease with PTX-100, then they could potentially be treated at a higher dose sooner rather than later and have the stamina and mental fortitude to stay on such a trial. The following graphs show the duration of the PFS period across the three indications, which highlights how CTCL patients exhibited a much longer 100% PFS period from the outset.
What this suggests to me is that perhaps PTCL and CTCL require different dosing regimes. I don't know... but the stats certainly bode well for advancement to Phase 2 in both indications, IMO. Will it requrie two separate arms or trials? I'm starting to think that a mixed label trial may be out of the question. A trial in PTCL based on a different dosage regime could well turn data across the broader subsets of PTCL.... so could PTX-100 for CTCL be pursued separately?
The data derived, based on the chosen trial design, can be picked to bits but at the end of the day, but the data will be assessed in context (the overall context) of the trial design. Sure, it will be up to the trial investigators to speculate themselves as to the next most approopriate trial design/s based on this data and the last of the data to come in from the existing trial participants. However, I believe that we couldn't be in better hands given who are lead investigator is.
... Merry Christmas to you.
