The notion that all 65 or 66 Clover patients are alive at this point is likely more rumor than truth. The nasty nature of late-line, metastatic MSS is reason enough to question the "65 alive" idea. And half the patients are getting what most would characterize as a sub-optimal dose. But leronlimab works in mysterious ways, and since it has never really been studied properly in cancer, anything is possible. While I doubt that all patients enrolled in the Clover trial are currently alive, I do believe leronlimab has an MOA that could keep patients alive for much longer than oncologist's might think. That would be a long period of disease stabilization, leading into a substantial survivor's benefit. In other words, managing, not curing, metastatic colorectal cancer. I've stated that the Clover trial probably has some surprises in store for us... this would certainly qualify, if true.
How might leronlimab manage cancer? First, by shutting down metastasis. Nothing new here; but, as Dr J reminds us, metastatic disease is what kills patients. So look for extended survivorship right there.
Clover patients are metastatic, after all. With existing lesions. But leronlimab is very active in the two organs where metastasis tends to seed itself--in the liver and the lungs. CCR5 is over-expressed in stellate hepatocytes in the liver, and epithelial cells in the lungs. Leronlimab reduces fibrosis. Calms RANTES and CCL3 signaling in both organs. Healthier livers, healthier lungs... healthier lives? Survivor benefit? I would lean that way... especially in regards to liver health. And we will be tracking the ALT numbers and other measures of liver health because clinicians always do. And since we are Cytodyn we are tracking chemokines in the blood, so high levels of CCL5 and CCL3 in the blood--post-leronlimab--indicate these ligands are not binding to their natural receptor. Because they are occupied. Case closed...
Dr Kasi tells us, in the Clover trial, that leronlimab makes patients feel better. Any clinical benefit here? Well, attenuating cachexia and relieving pressure/pain around the tumors helps ease the life of patients, helps them eat, and helps them stay on treatment schedules and maintain day-to-day activities. Priceless for late-line cancer patients. (This line of thought incorporates Geffry Forquerean's idea that leronlimab "treats the patient as well as the disease." Very germane to the topic at hand, and a generally under-appreciated benefit of leronlimab as a cancer therapeutic).
Will this provide a survival benefit? Hard to determine with any degree of precision... but chemo can't kill cancer if you are too sick from the chemo or the cancer to take it--so I'd say yes.
The following is rank speculation on my part... But I'm just going to go with it. The 17% ORR is lower that I expected. Like many on this board, I expect that number to rise with a) time, and b) the patients on the 700mg dose catching up to the patients on the 350mg dose. But still, doubling the 17% figure to a 35% ORR doesn't come close to that 60% ORR in the basket trial. And leronlimab seems to be a pretty consistent drug. So I would say there is an anomaly here... A discrepancy. 17% vs 60%. Might this be explained by a substantial number of patients classified as Stable Disease--whose tumors haven't shrunk the 30% necessary to qualify as a Partial Response--yet receive clinical benefit? And the clinical benefit manifests itself as survival?
Another way of saying this is the ORR metric does not pick up the survival benefit. Look at the 3 patients who exited the trial to pursue surgery. One of these patients qualified as a PR; where do you fit in the other two in terms of trial metrics? ORR-No! OS-Yes! SD-? PRS-??
Not much talk about Progression Free Survival on the board... But that might be the metric to watch. Let's say we triple the PFS... say 15 months. And that leads to triple or quadruple OS. I'd call that a huge first step forward in the management of colorectal cancer. And PFS may capture that, or even predict it. If PFS is associated with extended OS, we have a revolutionary cancer therapeutic on our hands. And we don't rely on an ICI for anything in the above scenario. (Oh, you want to cure cancer rather than manage it? Stay tuned, Cytodyn might have something there for you, too).
OS numbers will be preliminary at ASCO. And the ORR numbers will likely be maturing as well. But if my logic holds, I think we will see knockout PFS and SD numbers in mCRC that will get the attention of every oncologist. And Big Parma too.
One final thought--to PSU77 and the whole board--let's nail down this rumor, one way or another. I can't imagine "65 alive," given that half the Clover patients were on the 350mg dose. But rumors can be destructive... especially in small tight groups. So let's get to the bottom of this one post-haste! But as I've gone on at some length to suggest, there is a therapeutic pathway where these patients could conceivably--even reasonably--all remain alive. We can only hope so much...
Oh--Evil Rabbit--no AI was utilized in the creation of this post. So you can read it in good conscience, without fear of being tainted by the contemporary world.
How might leronlimab manage cancer? First, by shutting down metastasis. Nothing new here; but, as Dr J reminds us, metastatic disease is what kills patients. So look for extended survivorship right there.
Clover patients are metastatic, after all. With existing lesions. But leronlimab is very active in the two organs where metastasis tends to seed itself--in the liver and the lungs. CCR5 is over-expressed in stellate hepatocytes in the liver, and epithelial cells in the lungs. Leronlimab reduces fibrosis. Calms RANTES and CCL3 signaling in both organs. Healthier livers, healthier lungs... healthier lives? Survivor benefit? I would lean that way... especially in regards to liver health. And we will be tracking the ALT numbers and other measures of liver health because clinicians always do. And since we are Cytodyn we are tracking chemokines in the blood, so high levels of CCL5 and CCL3 in the blood--post-leronlimab--indicate these ligands are not binding to their natural receptor. Because they are occupied. Case closed...
Dr Kasi tells us, in the Clover trial, that leronlimab makes patients feel better. Any clinical benefit here? Well, attenuating cachexia and relieving pressure/pain around the tumors helps ease the life of patients, helps them eat, and helps them stay on treatment schedules and maintain day-to-day activities. Priceless for late-line cancer patients. (This line of thought incorporates Geffry Forquerean's idea that leronlimab "treats the patient as well as the disease." Very germane to the topic at hand, and a generally under-appreciated benefit of leronlimab as a cancer therapeutic).
Will this provide a survival benefit? Hard to determine with any degree of precision... but chemo can't kill cancer if you are too sick from the chemo or the cancer to take it--so I'd say yes.
The following is rank speculation on my part... But I'm just going to go with it. The 17% ORR is lower that I expected. Like many on this board, I expect that number to rise with a) time, and b) the patients on the 700mg dose catching up to the patients on the 350mg dose. But still, doubling the 17% figure to a 35% ORR doesn't come close to that 60% ORR in the basket trial. And leronlimab seems to be a pretty consistent drug. So I would say there is an anomaly here... A discrepancy. 17% vs 60%. Might this be explained by a substantial number of patients classified as Stable Disease--whose tumors haven't shrunk the 30% necessary to qualify as a Partial Response--yet receive clinical benefit? And the clinical benefit manifests itself as survival?
Another way of saying this is the ORR metric does not pick up the survival benefit. Look at the 3 patients who exited the trial to pursue surgery. One of these patients qualified as a PR; where do you fit in the other two in terms of trial metrics? ORR-No! OS-Yes! SD-? PRS-??
Not much talk about Progression Free Survival on the board... But that might be the metric to watch. Let's say we triple the PFS... say 15 months. And that leads to triple or quadruple OS. I'd call that a huge first step forward in the management of colorectal cancer. And PFS may capture that, or even predict it. If PFS is associated with extended OS, we have a revolutionary cancer therapeutic on our hands. And we don't rely on an ICI for anything in the above scenario. (Oh, you want to cure cancer rather than manage it? Stay tuned, Cytodyn might have something there for you, too).
OS numbers will be preliminary at ASCO. And the ORR numbers will likely be maturing as well. But if my logic holds, I think we will see knockout PFS and SD numbers in mCRC that will get the attention of every oncologist. And Big Parma too.
One final thought--to PSU77 and the whole board--let's nail down this rumor, one way or another. I can't imagine "65 alive," given that half the Clover patients were on the 350mg dose. But rumors can be destructive... especially in small tight groups. So let's get to the bottom of this one post-haste! But as I've gone on at some length to suggest, there is a therapeutic pathway where these patients could conceivably--even reasonably--all remain alive. We can only hope so much...
Oh--Evil Rabbit--no AI was utilized in the creation of this post. So you can read it in good conscience, without fear of being tainted by the contemporary world.
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