RE:RE:RE:RE:One more look at the new 90 day optimized dataEven
25%-30% CR at 450 days is a much better result than that achieved by the FDA-approved Keytruda. The Theralase phase 2 results achieved so far look very positive given expectations.
"For the population of patients for whom bacillus Calmette-Gurin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended." Definitions, End Points, and Clinical Trial Designs for Non–Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group
Ashish M. Kamat , Richard J. Sylvester , Andreas Bhle , Joan Palou , Donald L. Lamm , Maurizio BrausiMark Soloway , Raj Persad , Roger Buckley , Marc Colombel , J. Alfred Witjes
Keytruda got approval with
18.86% CR at 12 months - a far cry from a "clinically meaningful"
30% at 12 months. This was down to
11% CR at 36 months and serious treatment related adverse effects occurred in
8% of patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555576/ enriquesuave wrote: In the Keytruda trial, 5 patients were droppe from the 101 who got treated as they had not met disease definition of BCG Unresponsive NMIBC as per FDA. The FDA can and should take into account these 7 anomalies in our data IMHO
"101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96)"
Having said that, my realistic expectations for data at 450 days is 30-45% CR. Could it be 25-35% perhaps, but it may also be 50-70% if all goes perfect from now on. But we see a 38% CR and a potential right now of 54% CR excluding all anomalies, if 2 PR patients also end up CR. All IMHO, but in time we shall hopefully get there.
Eoganacht wrote: Great analysis. 54% CR at 450 days is 24% higher than the FDA benchmark of 30% CR at 18 to 24 months which, according to ImmunityBio, was deemed "likely too high and may not be realistically achievable".
https://immunitybio.com/immunitybio-announces-over-24-months-median-duration-of-complete-remission-with-100-nmibc-cis-patient-survival-setting-a-new-magnitude-of-benefit-in-patients-with-bcg-unresponsive/
enriquesuave wrote: An analysis of NR patients in overall data on all 38 patients, we have
3 patients from PH1: 2 CR post 450 days ( who received an Optimized Treatment) and 1 NR ( non optimized treatment)who probably had metastatic disease prior to treatment undiagnosed. That 1 NR patient should have probably not been included in trial or data.
1st set of 12 PH2 patients who were undertreated by 39-85% of which 5 were wrongly dropped ( due error in trial criteria ) Only 7 were eligible after error to receive a second treatment, of which 4 got a second Optimized treatment. So 5 patients counted as NR should really be excluded in all fairness as they got severely undertreated and never received a second treatment whatsoever, but are counted as NR.
23 patients received an Optimized Treatment from the start. ( Optimizations can improve over time as learning curve progresses IMO). 1 patient who passed away from unrelated issue is counted as NR.
Normally should be treated as a patient who dropped out of trial, and not counted at all. All IMHO
So overall we have 7 patients who are counted as NR, but should normally not be counted at all So if they were not counted, data would be recalculated out of 31 patients. Just to give an example, our numbers at 450 days would look like 5 out of 13 patients would be CR Vs 5 out of 20. That would equate to 38.5% CR on evaluable patients vs 25%, plus 2 PR patients out of these same 13 for a potential CR of 54% at 450 days. All IMO of course . So with mistakes out of the way and Optimized Treatment improvements, we shall hopefully get to those kind of numbers over time. To be noted that the FDA will be made aware of all of these important details in their analysis of the data. All IMHO do your own DD I have done mine. GLTA
Eoganacht wrote: I changed the percentages to patient counts for the recent 90 day numbers for the:
23 patients enrolled and treated in Study II who received an optimized primary study treatment
CR = 12
PR = 4
Pending = 3
NR = 4
Potential CR = 82%
In the last newsletter there were 18 post-Aug 20 2020 optimized patients
CR = 8
PR = 2
Pending = 7
NR = 1
Potential CR = 94.4%
In the period between the two news releases 7 patients reached 90 days and 5 more patients were treated for a total of 12 patients. Of these 12 patients there were:
CR = 4
PR = 2
Pending = 3
NR = 3
Potential CR = 75%
Out of these 12 patients 3 patients (25%) were NR. The results of just these 3 patients accounts for the drop in 90 day potential CR. We will probably never know what happened with these 3 probably very sick and elderly patients but given where we are in the trial it will likely have little overall effect. If you flip a coin 12 times you won't likely get 6 heads and 6 tails. You might get 4 tails and 8 heads. But if you fip a coin 100 times it will be much closer to 50% heads and 50% tails. If those 3 patients had been CR or PR we would have a 90 day potential CR of 96% and the sp would have reached new heights IMHO. But this isn't the first time Theralase's sp has taken an unexpected and unwarranted hit.