Cel Sci Corporation (CVM)

[jamesnhansen]

An HLA article relevant to CelSci's P3 Trial

lightrock asks me about including "% Responding" in our CelSci OS calculator. Some participants in the P2 study showed strong response while others did not. CelSci's patent claims that it can reduce HLA — human leukocyte antigen — on the surface of tumor cells. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria. With HLA removed, the host's immune system will recognize that a tumor is something that should be attacked, like an infection.

If Multikine is effective at down-regulating HLA in tumors, the p3 trial should clearly show this...

or possibly not:

If the test arm is comprised of people who don't have HLA+ tumors, theoretically there should NOT be increased OS even if Multikine is actually working! So it is critical to know what percentage of the test arm is comprised of HLA+ tumors, hence warranting lightrock's focus on this issue. Therefore, in the P3 study, it will be critical to correlate any OS increases with the HLA expression (or diminishment thereof). Perhaps this is why the study design focuses on p < 0.05 rather than OS, per se. E.g., if only 10% of the test arm showed HLA was eliminated but 100% of that group was "cured" then the P3 trial would be a smashing success even though the OS was very low.

The ClinicalTrials.gov description doesn't exclude or include HLA testing prior to enrolling. So the test arm cohort very likely resembles the population of all neck cancers. So what is that percentage?

Here's a quote from a 2017 paper, which sheds some light on this question:

Altered HLA expression on the tumor cell surface has been described in a variety of human tumors, with percentages ranging from 60–90% expression in different human tumor types

As I continue to review this issue, I'm reaching two conclusions:

1. Many types of advanced cancers are HLA+, so MK will have many immediate off-label targets if approved.
2. If there is a higher percentage of Stage III/IVa vs. Stage III-only cancers in the test arm, the advanced cancers may actually respond better to the MK as they initially may present more HLA.

To summarize, I'm not going to modify the calculator to add a variable for % Responding. I'm going to assume that the test arm cohort is greater than 50% HLA+ matching the population at large because the enrollees were not pre-screened. This means that the OS is likely about twice as good (for the % responding group) than what will be finally reported for the whole test arm.

Again, I have confirmed with the company that markers such as HLA are being studied and will reported in the final paper.

Thank you lightrock for pointing out this critical aspect of the P3 study to me.

Cheers from a raining-again Oregon,

Jim