I've been impressed with how much mileage we are getting out of a single Phase 2 trial.
[color=var(--text)]Not only seeing if Leronlimab works with the SOC in probably the biggest single cancer indication out there (numbers wise, with unmet needs). But comparing two relevant doses, with the opportunity to see dose-response at work. And an extension available to those who respond to the drug, and the rollover option for those who do not. And a primary endpoint--ORR--that is kind of low-hanging fruit.[/color]
[color=var(--text)]We also get to see if it reliably raises PDL-1 numbers. Which it apparently does... and we'll have the data to prove how much. [/color][color=var(--text)]In the rollover part of the trial we get to test the prime and pair hypothesis--prospectively--in up to 12 patients very sick patients in that indication. Without waiting around for a separate study...[/color]
And all throughout the trial we are capturing data on every biomarker imaginable that relates to leronlimab's effects on mCRC as well as CCR5 biology in the cancer context. They will be pouring over that data for years... (The academics will be all over it--think CCR5 classes at the University). And if they can come up with a predictive biomarker for efficacy (say ctDNA), then we are off to the races. And if we can pluck a biomarker associated with metastasis out of the Creatv or Natera data, it's game over! That, ultimately, is what I think they are after... once we get proof on the LL/ICI combo.
How did Dr J and the team get all this blessed by the FDA? No doubt having Dr Kasi on board was a part of this, and the early ctDNA declines are convincing. (Lalezari's comment about the data doing the talking now certainly applies here). But it all seems clear that the FDA has come around and is more receptive to "adoptive" trial design these days. So the timing on this for Cytodyn is great... But no doubt Dr J called in any and every favor anyone might have owed him to make this happen. And he is a pretty sharp cat, and a persuasive one at that.
My69's point that doing a dedicated trial with an ICI first "would simply confound Cytodyn's data" is accurate. Although in one interview Dr J did suggest he expected to trial the combo, or essentially go straight to an ICI if a patient progressed during the trial. Perhaps the negotiations that led to the Clover protocol will be discussed at some future point, and we'll see what exactly happened. Maybe the FDA actually leaned on Cytodyn a bit, and Lalezari went along? All I can say is all's well that ends well.
Now, Ken Chowder and Misiu might very well be quick to say that it didn't end well for those who passed. That is true. But there is no certainty that as 3rd-line mCRC patients--quite sick--the leronlimab/ICI combo would have saved their lives. Just assuming so carries the implication that we can extrapolate the 5 out of 5 TNBC survivors to another deadly cancer, with a different biology, and a larger patient pool. I do not know the ages of the Ladies of Leronlimab; but age and health status may very well have played a part in their survival. We do not know. And part of the Clover trial is to find out what Leronlimab can and can't do.
And please, do not forget human agency in all this. Both the choice to enter the trial in the first place, and to stay with it as the trial proceeds. There are other investigational drug trials available for 3rd-line mCRC patients. And right-to-try options. If I was part of the Clover trial and progressed but managed to get my PDL-1 numbers up, I would jump ship right away. And by that I mean not wait around for the rollover, and get an ICI somewhere, somehow, some way! That might very well have already happened. Anyway, criticizing Dr J and Cytodyn for basically taking direction from the FDA, and learning all we can about the ultimate relevance of LL as part of a new standard of care in mCRC, under the assumption that LL and an ICI is going to save EVERYONE... or perhaps even the majority of these sick patients... That is likely misplaced.
Finally, completing Clover-as-designed will provide plenty of vital information to guide oncologists in their use of Leronlimab as part of a new SOC in the very near future. How many lives will that save? That is the great cosmic question I haven't heard posed by anyone here or on Livimmune. For the religious, isn't that a question for the man upstairs with the Big Ledger? Down here, go ahead and calculate it out, if you like. It is not my place. Look, I feel uncomfortable talking about life and death like this... Exposed. But these things need to be talked about openly, with all respect and prayers for lives lost. And urgency for lives to save.
Yes, patients are going to die in this trial. Clover seems to offer them a remarkable amount of options and agency as they proceed on their journey, and face their destiny. I don't know a trial that has offered as much.
[color=var(--text)]Not only seeing if Leronlimab works with the SOC in probably the biggest single cancer indication out there (numbers wise, with unmet needs). But comparing two relevant doses, with the opportunity to see dose-response at work. And an extension available to those who respond to the drug, and the rollover option for those who do not. And a primary endpoint--ORR--that is kind of low-hanging fruit.[/color]
[color=var(--text)]We also get to see if it reliably raises PDL-1 numbers. Which it apparently does... and we'll have the data to prove how much. [/color][color=var(--text)]In the rollover part of the trial we get to test the prime and pair hypothesis--prospectively--in up to 12 patients very sick patients in that indication. Without waiting around for a separate study...[/color]
And all throughout the trial we are capturing data on every biomarker imaginable that relates to leronlimab's effects on mCRC as well as CCR5 biology in the cancer context. They will be pouring over that data for years... (The academics will be all over it--think CCR5 classes at the University). And if they can come up with a predictive biomarker for efficacy (say ctDNA), then we are off to the races. And if we can pluck a biomarker associated with metastasis out of the Creatv or Natera data, it's game over! That, ultimately, is what I think they are after... once we get proof on the LL/ICI combo.
How did Dr J and the team get all this blessed by the FDA? No doubt having Dr Kasi on board was a part of this, and the early ctDNA declines are convincing. (Lalezari's comment about the data doing the talking now certainly applies here). But it all seems clear that the FDA has come around and is more receptive to "adoptive" trial design these days. So the timing on this for Cytodyn is great... But no doubt Dr J called in any and every favor anyone might have owed him to make this happen. And he is a pretty sharp cat, and a persuasive one at that.
My69's point that doing a dedicated trial with an ICI first "would simply confound Cytodyn's data" is accurate. Although in one interview Dr J did suggest he expected to trial the combo, or essentially go straight to an ICI if a patient progressed during the trial. Perhaps the negotiations that led to the Clover protocol will be discussed at some future point, and we'll see what exactly happened. Maybe the FDA actually leaned on Cytodyn a bit, and Lalezari went along? All I can say is all's well that ends well.
Now, Ken Chowder and Misiu might very well be quick to say that it didn't end well for those who passed. That is true. But there is no certainty that as 3rd-line mCRC patients--quite sick--the leronlimab/ICI combo would have saved their lives. Just assuming so carries the implication that we can extrapolate the 5 out of 5 TNBC survivors to another deadly cancer, with a different biology, and a larger patient pool. I do not know the ages of the Ladies of Leronlimab; but age and health status may very well have played a part in their survival. We do not know. And part of the Clover trial is to find out what Leronlimab can and can't do.
And please, do not forget human agency in all this. Both the choice to enter the trial in the first place, and to stay with it as the trial proceeds. There are other investigational drug trials available for 3rd-line mCRC patients. And right-to-try options. If I was part of the Clover trial and progressed but managed to get my PDL-1 numbers up, I would jump ship right away. And by that I mean not wait around for the rollover, and get an ICI somewhere, somehow, some way! That might very well have already happened. Anyway, criticizing Dr J and Cytodyn for basically taking direction from the FDA, and learning all we can about the ultimate relevance of LL as part of a new standard of care in mCRC, under the assumption that LL and an ICI is going to save EVERYONE... or perhaps even the majority of these sick patients... That is likely misplaced.
Finally, completing Clover-as-designed will provide plenty of vital information to guide oncologists in their use of Leronlimab as part of a new SOC in the very near future. How many lives will that save? That is the great cosmic question I haven't heard posed by anyone here or on Livimmune. For the religious, isn't that a question for the man upstairs with the Big Ledger? Down here, go ahead and calculate it out, if you like. It is not my place. Look, I feel uncomfortable talking about life and death like this... Exposed. But these things need to be talked about openly, with all respect and prayers for lives lost. And urgency for lives to save.
Yes, patients are going to die in this trial. Clover seems to offer them a remarkable amount of options and agency as they proceed on their journey, and face their destiny. I don't know a trial that has offered as much.
6
