I read somewhere--probably one of the PRs--that pa

I read somewhere--probably one of the PRs--that patients didn't have to take the ICI concurrently with leronlimab to gain a benefit... What was important was that patients received LL first, it changed the tumor microenvironment and raised PD-L1 levels, and then the ICI could go to work on the inflamed tumors. Instead of trying to track down the citation, let me refer you to something more recent--Dr Lalezari's comments in the Karen Jagoda interview about "timelines." (Thanks KenChowder for cutting and pasting the transcript here on IH).

Jay Lalezari: "Well, we do not know a lot about the timelines. The one patient who's a long-term survivor and has been on leronlimab and a checkpoint inhibitor called atezolizumab for five years, the other four were on leronlimab for a period of time, then on a checkpoint inhibitor for a period of time."

These are the Ladies Dr J is talking about, with four out of the five having stopped leronlimab for an unknown period of time before receiving an ICI. So when you say "I guess dropping out of the trial (= no more leronlimab) would turn the hot tumor to a cold tumor again," well, that was an incorrect guess. What you described as a "suicidal move" turned out to be part of the process that saved their lives... because apparently a hot tumor stays hot. Hot enough for the ICI to work.

There is a lot we don't know about leronlimab and ICIs. Lalezari continued on in the interview to say "So we don't know what the timelines are of how long either drug would be required, and that's going to require the clinical studies to show us whether long-term maintenance is required or not." But at this stage of the game we do know leronlimab first, followed by an ICI... can save lives.

Our current trial is open label, and that implies patients are going to know what drugs and dose they are getting, as well as relevant CTC and PD-L1 numbers. If you are progressing on leronlimab but your PD-L1 numbers are up, wouldn't you drop out of the trial to get an ICI, if there are no provisions in the trial to give people the option?

I am hopeful for a clean, well-run clinical trial with few dropouts and good compliance from motivated patients. If the FDA decides not offer an ICI as part of the trial--after PD-L1 upregulation and upon progression--then I would expect many dropouts. Patients confronting life-and-death decisions, with all the stress and consternation that comes with those decisions. And less chance for the "unassailable" data we all seek. So the stakes are really huge for Cytodyn in this upcoming meeting... And they are huge for the FDA, too... for that matter. Not to mention they owe us one for the severe covid debacle...

I don't really have a clue how the FDA will decide this. It does occur to me that a future trial in first-line mCRC--with leronlimab and the SOC--would be a more appropriate venue to show off what leronlimab could do without being paired with an ICI right away... So FDA--make us do that kind of trial! Please!! But for this current trial with 3rd-line patients... no question in my mind they should get the ICI as soon as their PD-L1 numbers show they could benefit. And that is pretty much standard practice now, to give people ICI's when their PD-L1 numbers reach a certain level. So approving an ICI in this trial would be consistent with clinical practice. Let's freaking hope they do the right thing here...