RE: Short study patient options13 Oct 2023 08:44
@Bella, the original Phase 1a dose escalation study became a de facto Phase 1a/1b as multiple patients continued on treatment post-cohort, thus satisfying the dose expansion question about the safety and tolerability of longterm treatment - satisfying that thoroughly and starting to answer the efficacy question as well if patients stayed at their original dose level (tolerability and clinical effect at different dose levels).
Alan has said that the parallel study is a Phase 1a and I have no reason to doubt him, so again it is planned to be a dose escalation study examining safety and tolerability but at fortnightly dosing intervals. We started with MHRA approval - ?and FDA involvement as well. By the time the original Phase 1a was given permission to extend beyond 200mg/m² both the MHRA (max 400mg/m² restriction) and the FDA (max 25% dose escalations) were, as we now know, involved although only the MHRA giving permission was mentioned in the RNS. Alan has recently said the MHRA are slow, so they were obviously the rate-limiting step and, as Alan recently stated, the lead regulatory body is now the FDA and the trials have moved to the US.
Once the idea of more frequent dosing was floated it was clear that the FDA would not OK a Phase 2 fortnightly dosing study without being assured of the safety and tolerability of fortnightly dosing. Discussions are likely to have been going on for months (and hopefully in the broader context of applications for some or all of the FDA's regulatory streamlining goodies) and Avacta will have had the opportunity to provide data from existing patients at 2 weeks post-dosing. Nausea is subjective, retching, vomitting, diarrhea, constipation and alopecia are objectively observable. Blood count, liver function, kidney function, etc, etc can easily be tested. As regards the possibility of weekly dosing, maybe they thought that was a bridge too far at this stage or not necessary or they knew that the data they already had wouldn't support it or they floated it and the FDA slapped them down. Anyway, no matter how much 2-week data they had in the 3-week dosing study, it wouldn't answer the questions about safety and tolerability that a Phase 1a/1b study would provide, assuming patients again continue post-cohort as a surrogate for dose expansion.
When approved by the FDA, this parallel study's protocol will either be included in the existing one or will be a new entry in the ClinicalTrials database. Will they also take this opportunity to study fortnightly dosing of breast, ovarian, colorectal, etc cancers so as to get an indication of efficacy that might help in deciding Phase 2 dosing regimens for those cancers further down the line? We'll see - MSK has patients with all sorts of cancers.
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