Mmmmmm ... Maybe I don’t understand the science or the human psyche.
The information we just recived from Drs. J and Dr Hoffman is clear:
• Nealy all patents showed decline of ctDNA at week 2
• Median decrease ctDNA 350 mg Leronlimab cohort 70%
• Median decrease ctDNA 700 mg Leronlimab 90%
• 23/31 (74%) of patients with scans showed tumor shrinkage or classify as having stable disease
• Numeric increases of PDL-1 observed in majority of patients.
The obvious thing here ( very important) is to notice that there is a clear dose–response relationship (one of the strongest pharmacologic proofs of efficacy). Simply put: the FDA likes this because it greatly reduces concerns about placebo effects and random variations.
This, on itself is very good news. But there is more:
Reductions of ctDNA this magnitude >=80% means the patients are RESPONDERS (or, in some literature: likely super responders.)
But don’t take my word for it: a recent article (March 2025) by the British Journal of Cancer depicts patients with three “degrees” of ctDNA clearances and concludes: “our study revealed that early ctDNA variations and ctDNA clearance during the first course of CT (chemotherapy) were associated with treatment intensity in first-line mCRC patients, with a significant impact on prognosis.” This article refers to two studies with cohorts treated with two or three drugs and was undertaken to study the correlation between ctDNA clearance and patient prognosis. The conclusions apply to us.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12041588/
One can throw in the impressive numbers of improvements in mPFS and OS but we would be comparing apples with oranges (the drugs in the study are different), however the conclusion in any case is very clear: deep ctDNA clearance will demonstrate a significant impact on survival, more specifically:
Highest probability of radiologic tumor shrinkage, longest progression free survival (PFS), longest overall survival (OS), best long term disease control.
I wrote few weeks before that If leronlimab is effective, we should see:
• Rapid ctDNA decline (within 2–6 weeks)
• ctDNA clearance in responders
• ctDNA rebound in progressors
Why ??? because, as stated above, ctDNA correlates tightly with survival. This is not only from the paper above but, from multiple mCRC studies (SUNLIGHT, FRESCO 2), that show longer OS after deep ctDNA drops:
October and January will tell te tale.
Going back to human psyche. Apparently, this is not registering out there … the SP is "sleeping" or … am I misreading the data???
Don't think so.
GLTL
The information we just recived from Drs. J and Dr Hoffman is clear:
• Nealy all patents showed decline of ctDNA at week 2
• Median decrease ctDNA 350 mg Leronlimab cohort 70%
• Median decrease ctDNA 700 mg Leronlimab 90%
• 23/31 (74%) of patients with scans showed tumor shrinkage or classify as having stable disease
• Numeric increases of PDL-1 observed in majority of patients.
The obvious thing here ( very important) is to notice that there is a clear dose–response relationship (one of the strongest pharmacologic proofs of efficacy). Simply put: the FDA likes this because it greatly reduces concerns about placebo effects and random variations.
This, on itself is very good news. But there is more:
Reductions of ctDNA this magnitude >=80% means the patients are RESPONDERS (or, in some literature: likely super responders.)
But don’t take my word for it: a recent article (March 2025) by the British Journal of Cancer depicts patients with three “degrees” of ctDNA clearances and concludes: “our study revealed that early ctDNA variations and ctDNA clearance during the first course of CT (chemotherapy) were associated with treatment intensity in first-line mCRC patients, with a significant impact on prognosis.” This article refers to two studies with cohorts treated with two or three drugs and was undertaken to study the correlation between ctDNA clearance and patient prognosis. The conclusions apply to us.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12041588/
One can throw in the impressive numbers of improvements in mPFS and OS but we would be comparing apples with oranges (the drugs in the study are different), however the conclusion in any case is very clear: deep ctDNA clearance will demonstrate a significant impact on survival, more specifically:
Highest probability of radiologic tumor shrinkage, longest progression free survival (PFS), longest overall survival (OS), best long term disease control.
I wrote few weeks before that If leronlimab is effective, we should see:
• Rapid ctDNA decline (within 2–6 weeks)
• ctDNA clearance in responders
• ctDNA rebound in progressors
Why ??? because, as stated above, ctDNA correlates tightly with survival. This is not only from the paper above but, from multiple mCRC studies (SUNLIGHT, FRESCO 2), that show longer OS after deep ctDNA drops:
October and January will tell te tale.
Going back to human psyche. Apparently, this is not registering out there … the SP is "sleeping" or … am I misreading the data???
Don't think so.
GLTL
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