In an earlier post I put myself in the shoes of a fictional cancer patient who was accepted into the mCRC trial and randomized to the 350mg cohort. It’s not an ideal situation to get what you know is a substandard dose when you are fighting for your life… But you work with the hand you are dealt. In this hypothetical situation, I shifted my immediate goal from hoping for some benefit from leronlimab to figuring out how to increase my PD-L1 numbers so I can qualify for an ICI. I know from keeping up with the news that the mRNA covid vaccine has been shown to boost PD-L1 numbers significantly. (Grippen, Nature, Oct 2025). So my first act is to get the covid mRNA shot. Like right away.
If I am randomized to the 700mg dose I will flat out jump for joy! That dose gives me a real shot at deriving substantial benefit from the drug, with a partial or complete response not out of the question. And if I should progress, there is an ICI waiting in the wings. Given that 15 out of 17 patients boosted their PD-L1 numbers significantly at the 525mg or 700mg dose in the early trials, the odds are quite good that I will too. I’d call it a Win Win situation—if you get the 700mg dose.
There are certainly reasons an individual might refuse or delay an ICI, even on the 700mg dose and with elevated PD-L1 numbers. Perhaps you are feeling exceptionally well, the tumors are shrinking, and your CTCs and CAML numbers have dropped (which is predictive of a therapeutic response). So why not stay the course? Some will not want to take an ICI to avoid side effects. In consultation with a surgeon, some may delay an ICI if their primary tumor is shrinking to the point where it can be resected. Perhaps the anti-inflammatory benefits of leronlimab are substantial for some patients, and they will choose to just feel good for a while, without the ICI. And leronlimab can continue to do its thing, neutralizing metastasis and angiogenesis while providing “host-directed,” anti-inflammatory benefits to the patient. (For our trial, note that Crohn’s disease and ulcerative colitis are risk factors for CRC, and theoretically leronlimab should help calm the gut if those conditions are at play in an individual’s case).
And if the situation deteriorates… bring on the ICI. The 700mg dose of leronlimab and its ability to raise PD-L1 numbers quickly means the LL/ICI combo can be seen as the ultimate safety net for cancer… a kind of backstop or ace-in-the-hole if and when things turn. I suspect the timing of all this is going to be crucial—you don’t really want to be playing “chicken” with the PD-L1 numbers for too long. But just having the LL/ICI combo as an ace-in-the-hole will give patients a tremendous sense of security and faith in their course of treatment.
The numbers from the CreatvBio tests have revealed how quickly leronlimab works. Frequent testing in the early stages of treatment—say even weekly within the first couple of months—should be able to identify and predict those who are at extra risk and in need of rapid LL/ICI treatment. I don’t know if that kind of intensive monitoring is going on in our trial, but if so it could materially help those in the 350mg cohort. If they got their covid mRNA shot—or if the DSMB sees fit to bump them up to 700mg early in the process—there could be long-term survivors in the 350mg cohort. Sure hope so… But they are the ones I worry about.
If I am randomized to the 700mg dose I will flat out jump for joy! That dose gives me a real shot at deriving substantial benefit from the drug, with a partial or complete response not out of the question. And if I should progress, there is an ICI waiting in the wings. Given that 15 out of 17 patients boosted their PD-L1 numbers significantly at the 525mg or 700mg dose in the early trials, the odds are quite good that I will too. I’d call it a Win Win situation—if you get the 700mg dose.
There are certainly reasons an individual might refuse or delay an ICI, even on the 700mg dose and with elevated PD-L1 numbers. Perhaps you are feeling exceptionally well, the tumors are shrinking, and your CTCs and CAML numbers have dropped (which is predictive of a therapeutic response). So why not stay the course? Some will not want to take an ICI to avoid side effects. In consultation with a surgeon, some may delay an ICI if their primary tumor is shrinking to the point where it can be resected. Perhaps the anti-inflammatory benefits of leronlimab are substantial for some patients, and they will choose to just feel good for a while, without the ICI. And leronlimab can continue to do its thing, neutralizing metastasis and angiogenesis while providing “host-directed,” anti-inflammatory benefits to the patient. (For our trial, note that Crohn’s disease and ulcerative colitis are risk factors for CRC, and theoretically leronlimab should help calm the gut if those conditions are at play in an individual’s case).
And if the situation deteriorates… bring on the ICI. The 700mg dose of leronlimab and its ability to raise PD-L1 numbers quickly means the LL/ICI combo can be seen as the ultimate safety net for cancer… a kind of backstop or ace-in-the-hole if and when things turn. I suspect the timing of all this is going to be crucial—you don’t really want to be playing “chicken” with the PD-L1 numbers for too long. But just having the LL/ICI combo as an ace-in-the-hole will give patients a tremendous sense of security and faith in their course of treatment.
The numbers from the CreatvBio tests have revealed how quickly leronlimab works. Frequent testing in the early stages of treatment—say even weekly within the first couple of months—should be able to identify and predict those who are at extra risk and in need of rapid LL/ICI treatment. I don’t know if that kind of intensive monitoring is going on in our trial, but if so it could materially help those in the 350mg cohort. If they got their covid mRNA shot—or if the DSMB sees fit to bump them up to 700mg early in the process—there could be long-term survivors in the 350mg cohort. Sure hope so… But they are the ones I worry about.
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