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just curious if bevacizumab was held to the extreme scrutiny and lack of bevacizumab only arm that leronlimab has. which probably means that bevacizumab was comboed with standard of care protocol and showed a p-value worthy of improvement enough to approve?

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TAS-102 had approval and was standard of care in refractory CRC. The phase 2 and phase 3 trials ran a TAS-102 arm against a TAS-102/bevacizumab arm. Results were statistically significantly better in the combination of both drugs.

The downside is that TAS-102 has a large amount of awful side effects mainly lowered immune response neutrophils, which increases a bit with the combo therapy. I have to wonder whether TAS-102 is not highly specific to tumor cells as thought and might kill neutrophils or affect their production in the bone marrow. blocks VEGF inhibiting angiogenesis, leronlimab downregulates it and is also very effective in fighting angiogenesis, so bevacizumab may add nothing. TAS-102 works by breaking tumor cell DNA killing the cell. Leronlimab stops DNA repair killing tumor cells, can act to lower tumor cell reproduction and increase tumor fighting macrophages. Can leronlimab act as effectively in tumor cell death as TAS-102? Possibly and if leronlimab is equal to both drugs they can be eliminated and the side effects go away. The downside is that in a combo trial it will be hard to parse out what effects are due to leronlimab and what are due to the other drugs.