One of the things that’s been missing from our conversation about the trial protocol is human agency within the trial process. And the “lived experience” of being in a trial—how you feel, are you progressing, what are the side effects like… even what is your support system like? Ultimately it all comes down to a series of decisions the patient makes at different stages of the process, based on data, advice from the oncologists, and how you feel day-to-day. What is it like to be sitting in your oncologist’s office, dealing with these kind of consequential options and the decisions you need to make?
As a thought experiment I put myself in the shoes of a cancer patient in our trial and worked through some scenarios involving different doses and different responses to the drug. It is an open-label trial, so the information is out there. I’ll break it down into the 350mg cohort and the 700mg cohort and based on the limited knowledge we have about those doses I'll try and extrapolate some scenarios a patient might encounter.
I don’t have any special experience in clinical trials. But I am a cancer survivor—stage III MSS colorectal, locally advanced. So my focus on the trial protocol isn’t some academic exercise. I know what it’s like to go through surgery and oxaliplatin and capecetabine, and leronlimab looks like a much better option, and that is why I am here and invested. For humanity as well as my retirement! Believe me, I am a lucky guy—as of Sept I am 3 years cancer free. But we all know this shit has a way of returning. So I want to know everything I can about how leronlimab works in metastatic colorectal cancer.
But I certainly don’t want anybody in the trial to die for that knowledge! I think the changes to the trial protocol—if they are approved by the FDA--should give everyone in the 700mg group a good shot at life. If they progress during the trial and their PD-L1 numbers go up they will get an ICI. And if they respond, and the major tumor is shrinking and the CTCs/CAMLs are dropping, why not continue on with leronlimab in the rollover trial? No doubt you will be extensively monitored, and if the cancer never resolves or comes back, then you’ve got the ICI in your back pocket. Not a bad thing to have in your back pocket! In the meanwhile, why go through the side effects of Keytruda if you don’t have to?
If the luck of the draw gives me the 350mg dose I’d be bummed. But lie down and give up—hell no! At the 350mg dose, I am aware that my likely benefit from leronlimab is low, and so immediately my goal changes from getting a response and shrinking tumors to getting my PD-L1 numbers up to qualify for ICI treatment. The first thing I would do is get an MNRA vaccine, because it increases PD-L1 numbers in the cancer context. Turns cold tumors hot, you might say. Eventually it might mean dropping out of the trial if it comes to that, if the 350mg dose and the mRNA vaccine boosts my numbers enough (and the FDA/DSMB doesn’t ok an ICI within the trial timeframe). In the Nature article cited below I didn’t see how much the vaccine improved the PD-L1 numbers, but will note that it pumps up the IFN-y response and that is at least one of the MOAs by which leronlimab boosts PD-L1 in the tumor microenvironment. The mOS numbers from a retrospective look at 180 patients being treated for advanced NSCLC and melanoma at MD Anderson are quite good. Anyone who received the vaccine within 100 days of initiating an ICI almost doubled mOS—37 months vs 20 months in advanced cases. I’m a rational man, and reason suggests that—with the 350mg dose—if I want to live I’d better get my PD-L1 numbers up, somehow, and become eligible for an ICI. As far as I know the best shot at “somehow” is the mRNA vaccine. And the 1 year survival rate for SOC in the mCRC indication is 43%… so the clock is certainly ticking.
(Grippen, Nature, Oct 22, 2055, “SARS-COV-2 mRNA vaccines sensitize tumors to immune checkpoint blockade”)
With that perspective, why stay in the trial? Because I am getting state-of-the-art information about my cancer from the LifeTrax/Creatv Bio tests which I doubt I could get anywhere else. This includes the vital PD-L1 info and whether or not the 350mg dose plus SOC is doing anything, in my unique body. Recall that leronlimab works quickly and has predictive value. Like in 30 days (from the Adams/Creatv Bio study). So I will be following my CTCs/CAML numbers with interest, hoping they go down, as well as monitoring and checking in with the drug as to how it makes me feel (even tho it is a substandard dose there may be some tangible anti-inflammatory benefits). And finally--what is going to happen with the DSMB—are they going to eventually bump everyone up to the 700mg dose? All of the above are excellent reasons to hang in the trial. At least for six months or so, even if you are progressing. I'd say it’s the rational thing to do. But it is also rational to drop out of the trial if that is what it takes to get an ICI if your numbers rise and the FDA doesn’t approve amending the trial protocol. At this stage of the game, believe me, we are talking “by any means necessary.”
If you are in the 700mg cohort, why not just take the ICI as soon as you are eligible? I can think of three good reasons… But I’ll save that for another post, as this is running long. And I’ll run through potential options/scenarios for the 700mg cohort as well. Whose prospects look much better, of course, than the 350 mg cohort.
As a thought experiment I put myself in the shoes of a cancer patient in our trial and worked through some scenarios involving different doses and different responses to the drug. It is an open-label trial, so the information is out there. I’ll break it down into the 350mg cohort and the 700mg cohort and based on the limited knowledge we have about those doses I'll try and extrapolate some scenarios a patient might encounter.
I don’t have any special experience in clinical trials. But I am a cancer survivor—stage III MSS colorectal, locally advanced. So my focus on the trial protocol isn’t some academic exercise. I know what it’s like to go through surgery and oxaliplatin and capecetabine, and leronlimab looks like a much better option, and that is why I am here and invested. For humanity as well as my retirement! Believe me, I am a lucky guy—as of Sept I am 3 years cancer free. But we all know this shit has a way of returning. So I want to know everything I can about how leronlimab works in metastatic colorectal cancer.
But I certainly don’t want anybody in the trial to die for that knowledge! I think the changes to the trial protocol—if they are approved by the FDA--should give everyone in the 700mg group a good shot at life. If they progress during the trial and their PD-L1 numbers go up they will get an ICI. And if they respond, and the major tumor is shrinking and the CTCs/CAMLs are dropping, why not continue on with leronlimab in the rollover trial? No doubt you will be extensively monitored, and if the cancer never resolves or comes back, then you’ve got the ICI in your back pocket. Not a bad thing to have in your back pocket! In the meanwhile, why go through the side effects of Keytruda if you don’t have to?
If the luck of the draw gives me the 350mg dose I’d be bummed. But lie down and give up—hell no! At the 350mg dose, I am aware that my likely benefit from leronlimab is low, and so immediately my goal changes from getting a response and shrinking tumors to getting my PD-L1 numbers up to qualify for ICI treatment. The first thing I would do is get an MNRA vaccine, because it increases PD-L1 numbers in the cancer context. Turns cold tumors hot, you might say. Eventually it might mean dropping out of the trial if it comes to that, if the 350mg dose and the mRNA vaccine boosts my numbers enough (and the FDA/DSMB doesn’t ok an ICI within the trial timeframe). In the Nature article cited below I didn’t see how much the vaccine improved the PD-L1 numbers, but will note that it pumps up the IFN-y response and that is at least one of the MOAs by which leronlimab boosts PD-L1 in the tumor microenvironment. The mOS numbers from a retrospective look at 180 patients being treated for advanced NSCLC and melanoma at MD Anderson are quite good. Anyone who received the vaccine within 100 days of initiating an ICI almost doubled mOS—37 months vs 20 months in advanced cases. I’m a rational man, and reason suggests that—with the 350mg dose—if I want to live I’d better get my PD-L1 numbers up, somehow, and become eligible for an ICI. As far as I know the best shot at “somehow” is the mRNA vaccine. And the 1 year survival rate for SOC in the mCRC indication is 43%… so the clock is certainly ticking.
(Grippen, Nature, Oct 22, 2055, “SARS-COV-2 mRNA vaccines sensitize tumors to immune checkpoint blockade”)
With that perspective, why stay in the trial? Because I am getting state-of-the-art information about my cancer from the LifeTrax/Creatv Bio tests which I doubt I could get anywhere else. This includes the vital PD-L1 info and whether or not the 350mg dose plus SOC is doing anything, in my unique body. Recall that leronlimab works quickly and has predictive value. Like in 30 days (from the Adams/Creatv Bio study). So I will be following my CTCs/CAML numbers with interest, hoping they go down, as well as monitoring and checking in with the drug as to how it makes me feel (even tho it is a substandard dose there may be some tangible anti-inflammatory benefits). And finally--what is going to happen with the DSMB—are they going to eventually bump everyone up to the 700mg dose? All of the above are excellent reasons to hang in the trial. At least for six months or so, even if you are progressing. I'd say it’s the rational thing to do. But it is also rational to drop out of the trial if that is what it takes to get an ICI if your numbers rise and the FDA doesn’t approve amending the trial protocol. At this stage of the game, believe me, we are talking “by any means necessary.”
If you are in the 700mg cohort, why not just take the ICI as soon as you are eligible? I can think of three good reasons… But I’ll save that for another post, as this is running long. And I’ll run through potential options/scenarios for the 700mg cohort as well. Whose prospects look much better, of course, than the 350 mg cohort.
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