Thanks for bringing up those "basket trial" results, Dream Big. Those 5 patients are the only people in the world who have received leronlimab specifically for mCRC. Small numbers--OF COURSE--but I think it is important to take those results seriously, and dig a little deeper. As noted, 3 out of 5 patients had a Partial or Complete Response, for an Objective Response Rate of 60%. I will add that if you take out the single patient who received leronlimab as a monotherapy, you get 3 out of 4 patients with a Partial or Complete Response, for a ORR of 75%. In other words, the patients that got chemo with their Leronlimab did pretty well (note that 2 received Bev along with the FOLFOX and FOLFOXIRI chemo).
Something you pointed out that I hadn't noticed before--none of those patients received the 700 mg dose! All 5 received 525 or 350 mg... It has been a long weekend, and I don't want to dig up the poster, but do you know the breakdown of how many got 525 and how many got 350? That would tell us something...
And look at the Overall Survival numbers, and the range. 15.8 months OS, from 4.2 months to 57 months. If you make the assumption that the patient who survived 4.2 months was either the non-responder that got chemo, or got monotherapy, and evaluated the OS number for the other three, what would that tell us? Even better, strike both outliers--the 4.2 and 57 month survival numbers--and what would the OS number be? Whatever it is, that would tell us even more...
We do not know how sick these five patients were when the entered the trial. But we do know that patients in the Clover trial were pretty sick, according to Hoffman's recent presentation. So that is a very real wild card. And why the 60% ORR is unlikely to hold up.
And there is some pertinent information about CCR5 inhibition and chemo from the old Picasso trial, which paired maraviroc and Keytruda several years back, for mCRC. Progression-Free Survival of 2.1%, and an ORR of 5.3% were the headline numbers, and they are pretty poor. But apparently survivors of the initial treatment received chemo as salvage therapy--and they had a Disease Control Rate north of 70%. The thinking is that CCR5 inhibition primed the tumor for the chemo to do it's thing, and drove the respectable Overall Survivor number of 9.8 months (which is comparable to the SOC established later by Taz and Bev in the Sunlight trial). The abstract also provided the range for OS, and one survivor lived 20 months. Not bad for a sub-optimal CCR5 inhibitor, with chemo apparently doing the heavy lifting after the Keytruda/Leronlimab didn't do much as a combo.
We can speculate and argue about the 22 and the 43 and other tidbits of information about the Clover trial... But we do have some data on CCR5 inhibition in metastatic colon cancer that I suggest we take more seriously. The pairing of CCR5 inhibition with chemo clearly offers substantial clinical benefit. And we have small but rigorous, well thought-out trial that is about to tell us how much. Can't wait! And in the meanwhile, I continue to follow the science.
Here is the quote from the abstract, and a link (the paper itself is behind a paywall...):
"The feasibility rate was 94.7% [90% CI 77.4–99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68–2.30], median OS 9.83 months [95% CI, 5.59–20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS."
(By the way, eotaxin is also known as CCL11. Another potential biomarker in the mix! And while Cytodyn doesn't specifically mention tracking CCL11, AI tells me that it is a chemokine that is commonly measured in these sorts of trials. Hope so...).
https://www.sciencedirect.com/science/article...4922001617
Something you pointed out that I hadn't noticed before--none of those patients received the 700 mg dose! All 5 received 525 or 350 mg... It has been a long weekend, and I don't want to dig up the poster, but do you know the breakdown of how many got 525 and how many got 350? That would tell us something...
And look at the Overall Survival numbers, and the range. 15.8 months OS, from 4.2 months to 57 months. If you make the assumption that the patient who survived 4.2 months was either the non-responder that got chemo, or got monotherapy, and evaluated the OS number for the other three, what would that tell us? Even better, strike both outliers--the 4.2 and 57 month survival numbers--and what would the OS number be? Whatever it is, that would tell us even more...
We do not know how sick these five patients were when the entered the trial. But we do know that patients in the Clover trial were pretty sick, according to Hoffman's recent presentation. So that is a very real wild card. And why the 60% ORR is unlikely to hold up.
And there is some pertinent information about CCR5 inhibition and chemo from the old Picasso trial, which paired maraviroc and Keytruda several years back, for mCRC. Progression-Free Survival of 2.1%, and an ORR of 5.3% were the headline numbers, and they are pretty poor. But apparently survivors of the initial treatment received chemo as salvage therapy--and they had a Disease Control Rate north of 70%. The thinking is that CCR5 inhibition primed the tumor for the chemo to do it's thing, and drove the respectable Overall Survivor number of 9.8 months (which is comparable to the SOC established later by Taz and Bev in the Sunlight trial). The abstract also provided the range for OS, and one survivor lived 20 months. Not bad for a sub-optimal CCR5 inhibitor, with chemo apparently doing the heavy lifting after the Keytruda/Leronlimab didn't do much as a combo.
We can speculate and argue about the 22 and the 43 and other tidbits of information about the Clover trial... But we do have some data on CCR5 inhibition in metastatic colon cancer that I suggest we take more seriously. The pairing of CCR5 inhibition with chemo clearly offers substantial clinical benefit. And we have small but rigorous, well thought-out trial that is about to tell us how much. Can't wait! And in the meanwhile, I continue to follow the science.
Here is the quote from the abstract, and a link (the paper itself is behind a paywall...):
"The feasibility rate was 94.7% [90% CI 77.4–99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68–2.30], median OS 9.83 months [95% CI, 5.59–20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS."
(By the way, eotaxin is also known as CCL11. Another potential biomarker in the mix! And while Cytodyn doesn't specifically mention tracking CCL11, AI tells me that it is a chemokine that is commonly measured in these sorts of trials. Hope so...).
https://www.sciencedirect.com/science/article...4922001617
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