The graphs are very interesting; some analysis of what I am presently understanding.
Comparison with SOC and SG from SG trial.
They have compared the results of LL against both SOC (chemo) and another drug's trial (Sacitizumab Govitecan). Most likely Cytodyn has used the SOC data from that trial. So that would be a firm reference point for our study, and not some adhoc numbers pulled out of a hat.
LL has done much better than SOC but either similar to or slightly better than SG (at least in certain identified subgroups)
Graph on Pg 6:
This shows the mPFS and mOS graph for SOC (the left column) and the SOC vs SG on the right column. (So the left column just separates out the SOC data in the right column and presents it separately).
SOC: mPFS = 2.3 months. (i.e. half of patients in the control SOC group of the SG trial had PFS <= 2.3 months (disease became worse within 2.3 mo) and half had > 2.3 (disease became worse only after 2.3 mo))
SOC: mOS = 6.6 months (half of the control group of SOC-only patients in the SG trial died within 6.6 months)
SG: mPFS = 5.6 mo. (half of SG patients in the SG trial had disease progression within 5.6 mo and half had only after 5.6 mo)
SG: mOS = 12.1 mo (half of SG patients in the SG trial survived over 12.1 mo and half died within ~ 1 year)
In the Summary Page 11,
the goals stated are that we want LL patients to have mPFS > 2.3 mo of the SOC or >5.6 of the SG trial; likewise goal of mOS>6.7 of SOC or >12.1 of SG.
Clearly we would like to be above the benchmarks of SG. If the SG trial leads to approval and it becomes the new SOC, then we would have to outperform it. However for now, at the least we need to do better than SOC.
However the purpose of our "trials" is first of all to figure out the ideal patient population on which LL will work best on. This is VERY important. Our 29 or 30 patients is a whole mix of unfiltered patients including both Compassionate eINDs and the phase 1b group. The SG trial would have been much more honed in on the group for whom they decided from their early phase trials their drug will work optimally. We are trying to do this now.
CCR5
Page 7 shows:
Among the patients (18 out of 29) who had CCR5 < 50% in tissue samples, Leronlimab+Carboplatin showed similar mPFS as SG. However for the 11 patients who had CCR5>= 50%, LL showed worse mPFS than SG. (It is not clear if the CCR5 % noted here is what is recorded before the treatment starts; after treatment starts, LL may impact the expression (?))
Their conclusion in the Summary Pg 11:
This correlation between LL efficacy in mPFS and the CCR5 expression suggests that LL works better on patients who initially had < 50% CCR5 expression.
However when it comes to mOS, there is no specific correlation with CCR5 expression that our data shows. Leronlimab seems to generally have mOS similar to SG.
The CAML data
In our trial 18 of 25 patients (72%) showed decrease in CAML after 1 cycle of LL treatment and 7 of 25 showed increase in CAML after 1 cycle.
Interestingly they found excellent improvement in both mPFS and mOS in the subgroup of patients who had CAML decrease after 1 cycle. That's where the 300% and 450% showed up; probably in comparison with SOC but from page 9 graphs, the OS for this subgroup is superior to SG as well. We may guess that in this group, many are surviving well past 12 months.
(Pg 9 graphs seems to suggest that patients having small CAMLs tend to do better with LL (and comparably with SG) than patients with large CAMLs. But I don't follow what that means. Is that an earlier stage of the cancer?)
All this information tells us the possibility that LL may prove to be best drug for patients who had CCR5 < 50% and who showed decrease in CAML after 1 month 1 cycle treatment with LL. Hopefully the FDA will look at this wealth of data and conclude that indeed we should do further trials and let us move forward in that direction.
If not for SG, our data would already be extremely compelling against the SOC that the SG trial was comparing its data against. "Unfortunately" for us, the bar seems to be set very high by SG though we may still have a subgroup of mTNBC patients for whom LL will work best. More importantly, if we can build off these initial results and show that LL is indeed a cancer fighter, then it also bodes well for our chances for the many other solid tumors that we hope our MOA works on.
