Phase 2 data. The final MM data was first presented by Dr. Agarwala in Munich on June 22 at At 2nd European Post-Chicago Melanoma Meeting 2012. See the PR here. There some slight differences from the data presented in Vienna on October 1 that may be gleaned from comparing the two PRs. These appear negligible or immaterial:
- An Objective Response Rate of 51% (v. 50% in Munich) in subjects' target lesions (25% Complete Response and 26% Partial Response [v. 25%]);
- 69% disease control (v. 70%) in these lesions (combined Complete, Partial and Stable Response subjects); and
- Stage III subjects experienced a substantially higher target lesion response rate (60% OR [v. 58%] and 79% [v. 81%] disease control) versus Stage IV subjects (22% and 33%, respectively);
- Analysis of temporal data showed that Stage III subjects also experienced significantly greater mean Progression Free Survival (PFS) of at least 9.7 [v. 9.6] months, versus 3.1 months for Stage IV subjects (median PFS for Stage III subjects was not reached during the 12-month study interval).
Overall, the Phase 2 data was very strong, particularly for Stage III subjects, who will be the patient population for the Phase 3 trial. It was striking to net out those subjects experiencing early progression prior to the week 8 assessment who were then classified as non‐evaluable (NEV): 66% OR -- two-thirds of subjects -- and 88% disease control -- nearly 9 in 10 subjects, assuming my process and math is correct. The PFS curve is very similar when netting out NEV, although it does improve.
What is even more striking is the expectation the Phase 3 trial will improve further -- Phase 2 bested Phase 1, and now Phase 3 is expected to best Phase 2 -- since Phase 3 investigators will be able to treat all lesions.
The finalization of this data bodes well for its long-awaited publication in The Lancet in 2012.
ESMO poster. The poster itself had a few other useful nuggets. First, the Australian combination therapy study of intralesional PV-10 plus radiotherapy by Foote et al. had enrolled 7 patients as of July. The recent rumor of a double digit number of patients enrolled in the trial makes sense.
Second, the start of the human MOA study by Moffitt was imminent as of the submission of the poster.
Phase 3 trial design. I had thought Dr. Agarwala's Munich presentation had contained the final design. I was incorrect. I am led to believe there is no more negotiating or discussion with the FDA on the trial design, which makes sense. The Vienna PR goes into great detail about the design parameters, as contrasted with the Munich PR, which did not mention any meaningful aspect of the trial design.
The second quote attributed to Eric in the trial design section of the PR is telling. In particular: "This study is designed to demonstrate delay or avoidance of progression of melanoma from a locoregional disease to a life-threatening systemic stage." PV-10 treats disease so well, there will be much less Stage IV disease. Melanoma will not spread to visceral organs because the drug would have stopped it before it does.
There would appear to be no doubt the Phase 3 trial will hit is primary endpoint of PFS. If Provectus hits the same PFS in Phase 3 as the company did in Phase 2, the endpoint is reached. The contemplated hazard ratio dictates almost 6 months PFS for PV-10 versus just less than 3 months for DTIC/TMZ.
The 4-week clinical response assessment (in addition to the 12-week full response assessment) is interesting new design parameter. It is an excellent way for Provectus to measure how effective PV-10 is versus DTIC/TMZ as the study progresses (i.e., a very clear picture of trial success as early as 1Q13 or 2Q13).