House of Cards--
I agree with the general thrust of your comments--the Overall Response Rate of 6.3% in the SOC in 3rd-line mssCRC seems like low-hanging fruit that leronlimab should be able to handily beat. Your question about whether the numbers will justify a BTD or AA... well, that's to be determined and is above my pay-grade. But I'm optimistic about the trial, and I think positive results will force the DSMB to make some life and death decisions.
In Cytodyn's July 1st press release about the Barcelona ESMO conference, we learned that 3/5 mss CRC patients had a partial or complete response. If those numbers hold up we are talking about an ORR of 60%! And even if leronlimab lets us all down and only 1/5 patients have a PR or CR... well, that still basically triples the ORR of the SOC.
(Not a medical student, so I actually had to look up the definition of ORR before writing this. So FYI, the ORR is the percentage of patients in a trial that have a complete or partial response. That makes the ORR a very meaningful end point in a trial. I did wonder, do they include metastatic tumors in the calculation of "tumor burden," in addition to the primary tumor? And indeed they do. And my final question--how do they define a partial response?--and that would be a reduction of 30% of the individual tumor, whether primary or metastatic).
Unlike CD12, which was sabotaged from the beginning, I think this trial is designed for success. I'll go even further and say it is designed to put a great deal of pressure on the DSMB, when they are confronted with what I suspect will be blow-out numbers--(primarily from leronlimab's reduction in metastatic tumor burden). And they will have several issues to consider, with lives in the balance, on a thumbs up or thumbs down basis. Here's six questions, starting with the obligatory safety issues--
1) Is 350mg of leronlimab safe with the TAS-102/Bev SOC?
2) Is 700mg of leronlimab safe?
3) Should we transition everyone to the 700mg dose because people are progressing on 350?
4) For those that progress yet exhibit a substantial increase in PDL-1... should we give them an ICI?
5) And by the way, how much of an increase in PDL-1 do you get with 350mg?
(See numbers 2 and 3).
6) If the ORR is 20/40/60% should we stop the trial for overwhelming efficacy and transition everyone remaining to 700mg?
I'd say this is going to be a pretty important series of DSMB meetings. The data is going to put them on the spot. Under the gun. You wonder... at some point in the process will they realize they are at an inflection point in medical history? And will they realize their humanity is also under the microscope?
I think Cytodyn and leronlimab will rise to the occasion with this trial. Favorable endpoints, relevant biomarkers measured by Creatv, lots of supporting theory and clinical documentation. And the weight of the world on the DSMB. I think it's going to be like bringing an AK47 and a couple of hand grenades to a knife fight. Even the mighty DSMB will get blown away--By Unassailable Data.
I agree with the general thrust of your comments--the Overall Response Rate of 6.3% in the SOC in 3rd-line mssCRC seems like low-hanging fruit that leronlimab should be able to handily beat. Your question about whether the numbers will justify a BTD or AA... well, that's to be determined and is above my pay-grade. But I'm optimistic about the trial, and I think positive results will force the DSMB to make some life and death decisions.
In Cytodyn's July 1st press release about the Barcelona ESMO conference, we learned that 3/5 mss CRC patients had a partial or complete response. If those numbers hold up we are talking about an ORR of 60%! And even if leronlimab lets us all down and only 1/5 patients have a PR or CR... well, that still basically triples the ORR of the SOC.
(Not a medical student, so I actually had to look up the definition of ORR before writing this. So FYI, the ORR is the percentage of patients in a trial that have a complete or partial response. That makes the ORR a very meaningful end point in a trial. I did wonder, do they include metastatic tumors in the calculation of "tumor burden," in addition to the primary tumor? And indeed they do. And my final question--how do they define a partial response?--and that would be a reduction of 30% of the individual tumor, whether primary or metastatic).
Unlike CD12, which was sabotaged from the beginning, I think this trial is designed for success. I'll go even further and say it is designed to put a great deal of pressure on the DSMB, when they are confronted with what I suspect will be blow-out numbers--(primarily from leronlimab's reduction in metastatic tumor burden). And they will have several issues to consider, with lives in the balance, on a thumbs up or thumbs down basis. Here's six questions, starting with the obligatory safety issues--
1) Is 350mg of leronlimab safe with the TAS-102/Bev SOC?
2) Is 700mg of leronlimab safe?
3) Should we transition everyone to the 700mg dose because people are progressing on 350?
4) For those that progress yet exhibit a substantial increase in PDL-1... should we give them an ICI?
5) And by the way, how much of an increase in PDL-1 do you get with 350mg?
(See numbers 2 and 3).
6) If the ORR is 20/40/60% should we stop the trial for overwhelming efficacy and transition everyone remaining to 700mg?
I'd say this is going to be a pretty important series of DSMB meetings. The data is going to put them on the spot. Under the gun. You wonder... at some point in the process will they realize they are at an inflection point in medical history? And will they realize their humanity is also under the microscope?
I think Cytodyn and leronlimab will rise to the occasion with this trial. Favorable endpoints, relevant biomarkers measured by Creatv, lots of supporting theory and clinical documentation. And the weight of the world on the DSMB. I think it's going to be like bringing an AK47 and a couple of hand grenades to a knife fight. Even the mighty DSMB will get blown away--By Unassailable Data.
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