After chemo and the mabs, is regorafenib the treat

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After chemo and the mabs, is regorafenib the treatment for mCRC? If so, a trial pairing leronlimab with regorafenib that shows noticeably better results than what reforafenib has shown alone might lead to an accelerated approval.

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In the last phase 2 trial which was abandoned it was single arm so it would not have shown what leronlimab could do on it's own. The FDA would have insisted on a combination because the second proven drug would act as a failsafe in case leronlimab failed to have effect. The downside to that is leronlimab might get tagged with the adverse events of regorafenib and improvements might be attributed to the synergy of the combo and not leronlimab alone.

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Do we know how Cytodyn was planning to get regorafenib for this trial? Did they have a collaboration with Bayer?

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As an approved drug it might have been bought or Bayer may have donated it thinking improved outcomes might improve sales of their drug. Their drug could definitely use the help.

They had two phase three trials it seems like the FDA wanted the second one to better show the safety profile.

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Overall, 2,847 patients (99%) had at least one TEAE; TEAEs were regorafenib related in 2,613 patients (91%) (Table ​(Table3).3). The most frequent grade ≥3 regorafenib‐related TEAEs were hypertension (15%), HFSR (14%), fatigue (13%), diarrhea (5%), and hypophosphatemia (5%). Serious TEAEs occurred in 1,251 patients (44%) and were regorafenib related in 251 (9%).

Twenty‐three percent of patients (674/2,872) had PFS >4 months. Estimated PFS rates (95% CI) at 6, 9, and 12 months were 15% (14, 16), 8% (6, 9), and 4% (3, 5), respectively.

From first trial -

Median overall survival was 6·4 months in the regorafenib group versus 5·0 months in the placebo group

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369948/

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You may ask, - leronlimab downregulates VEGF, regorafenib inhibits VEGF why the worse safety profile of regorafenib?

Directly inhibiting a protein to a high degree can virtually shut down it's activities even if normal levels of activity are needed by the body to function properly. Leronlimab on the other hand only shuts down any increase caused by CCR5 the other CCR receptors allow the normal functions of those proteins.