Marizomib Fails a Phase 3 Clinical Trial in ndGBM Patients
Big Study. Muddy Biology. Ugh!
The results of a large Phase 3 RCT examining the utility of the brain-penetrant pan-proteasome inhibitor marizomib + TMZ/RT (followed by adjuvant TMZ) -versus- TMZ/RT alone (followed by adjuvant TMZ) (i.e. SoC for ndGBM patients) in a cohort of ndGBM patients were recently reported (see here; NCT03345095).
To quote the authors:
“Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.”
More Grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.
The dreaded Double Whammy: No improvement in mOS or mPFS against a background of significantly enhanced (S)AEs.
MissionGBM Commentary
With reference to Part 2 of the “Investing in Brain Cancer” series, if the biology has not been adequately elucidated, it is a good idea to STOP until the biology is understood. Scarce investment and patient resources can be directed elsewhere.