It will be useful to get clarification on study design and endpoints when the trial gets posted to clinical trials.gov. For now I am just suggesting Cytodyn may be going after PFS, not overall survival.
The following study from 2021 may be relevant:
“the combination of TAS-102 and bevacizumab was shown to extend the median PFS”
“The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety”
“The median PFS was 4.5 months; the median overall survival was 9.3 months.”
https://pubmed.ncbi.nlm.nih.gov/33083913/
Compare from the Cytodyn PR:
“This open label, randomized (1:1), multicenter trial will evaluate the anti-tumor activity (via overall response rate, ORR) of leronlimab at doses of 350 mg and 700 mg in combination TAS-102 and bevacizumab in approximately 60 patients with CCR5+, microsatellite stable metastatic CRC (mCRC).”
ORR is more likely to mean PFS, not OS.
Again, from the PR: “TAS-102 and bevacizumab will be administered for three of four weeks in a four-week cycle, and leronlimab (at doses of 350 mg or 700 mg) will be administered weekly. ”
I have looked at oncology regimens at the organization I work at involving bevacizumab and irinotecan etc …these regimens go for MANY more treatment cycles, implying again we are probably looking at PFS but I will let the protocol drop speak for itself as I am not an oncologist and we are not looking at first line therapy which is likely to have a longer treatment cycle series in the regimen.
Keep in mind, the linked trial here and Kabonk’s comment are not surgical for MSS. The Leronlimab trial will be. As such the results can not be compared directly, you would think they should be compared to PFS in a true comparison group that has failed initial treatment and is also MSS. MSS CRC is a bleak diagnosis where the treatment landscape is tantamount to the “Ohhhh Fudge” comment by Ralphie in The Christmas Story. The MSS population has a higher propensity toward metastasis and ergo a worse prognosis. I believe Bevacizumab is the only FDA approved VEG-F inhibitor that can be used as a first line treatment with chemotherapy. Anti-angiogenesis with a VEG-F inhibitor as an adjunct to cancer therapy makes sense and has been proven in trial data; as we know Leronlimab downregulates VEG-F but is acting in other important ways, such as the re-polarization of macrophages to anti-tumor. In short, I expect Leronlimab to move the needle and hopefully turn heads…investors, FDA, BP.
I would like to know study duration but am very suspicious of OS taking over a year…we are more likely kicking the tires on PFS. If the study results are highly compelling enough to make Ralphie eat his words it is not unreasonable to see Leronlimab paired in a phase 3 trial, likely under partnership.
Last comment is to respect the speed of the trial process…this is a multi-center trial, every trial site has to set up a budget, get contract paperwork inked, get IRB approval, principal investigator assigned, education on protocol for the nurses assisting blah blah blah. This trial is of extreme importance but I am expecting market moving news near term to come from a different quarter, namely the MASH mice results the end of September. All this is sauce for the goose and investors will be well fed, but respect the speed of the process.
The following study from 2021 may be relevant:
“the combination of TAS-102 and bevacizumab was shown to extend the median PFS”
“The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety”
“The median PFS was 4.5 months; the median overall survival was 9.3 months.”
https://pubmed.ncbi.nlm.nih.gov/33083913/
Compare from the Cytodyn PR:
“This open label, randomized (1:1), multicenter trial will evaluate the anti-tumor activity (via overall response rate, ORR) of leronlimab at doses of 350 mg and 700 mg in combination TAS-102 and bevacizumab in approximately 60 patients with CCR5+, microsatellite stable metastatic CRC (mCRC).”
ORR is more likely to mean PFS, not OS.
Again, from the PR: “TAS-102 and bevacizumab will be administered for three of four weeks in a four-week cycle, and leronlimab (at doses of 350 mg or 700 mg) will be administered weekly. ”
I have looked at oncology regimens at the organization I work at involving bevacizumab and irinotecan etc …these regimens go for MANY more treatment cycles, implying again we are probably looking at PFS but I will let the protocol drop speak for itself as I am not an oncologist and we are not looking at first line therapy which is likely to have a longer treatment cycle series in the regimen.
Keep in mind, the linked trial here and Kabonk’s comment are not surgical for MSS. The Leronlimab trial will be. As such the results can not be compared directly, you would think they should be compared to PFS in a true comparison group that has failed initial treatment and is also MSS. MSS CRC is a bleak diagnosis where the treatment landscape is tantamount to the “Ohhhh Fudge” comment by Ralphie in The Christmas Story. The MSS population has a higher propensity toward metastasis and ergo a worse prognosis. I believe Bevacizumab is the only FDA approved VEG-F inhibitor that can be used as a first line treatment with chemotherapy. Anti-angiogenesis with a VEG-F inhibitor as an adjunct to cancer therapy makes sense and has been proven in trial data; as we know Leronlimab downregulates VEG-F but is acting in other important ways, such as the re-polarization of macrophages to anti-tumor. In short, I expect Leronlimab to move the needle and hopefully turn heads…investors, FDA, BP.
I would like to know study duration but am very suspicious of OS taking over a year…we are more likely kicking the tires on PFS. If the study results are highly compelling enough to make Ralphie eat his words it is not unreasonable to see Leronlimab paired in a phase 3 trial, likely under partnership.
Last comment is to respect the speed of the trial process…this is a multi-center trial, every trial site has to set up a budget, get contract paperwork inked, get IRB approval, principal investigator assigned, education on protocol for the nurses assisting blah blah blah. This trial is of extreme importance but I am expecting market moving news near term to come from a different quarter, namely the MASH mice results the end of September. All this is sauce for the goose and investors will be well fed, but respect the speed of the process.
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