At long last, tremelimumab scores

Tremelimumab, the anti-CTLA4 antibody Astrazeneca had largely deprioritised after a string of clinical failures, suddenly has a success to its name. This is courtesy of the first-line NSCLC study Poseidon, which has reached its co-primary overall survival endpoint and shown a statistically significant benefit for an Imfinzi/treme/chemo triplet versus chemo alone. This is a broadly similar setting and approach to Bristol Myers Squibb’s Checkmate-9LA study, which secured US approval for an Opdivo/Yervoy/chemo triplet a year ago. However, tremelimumab has never before shown a survival benefit – and Poseidon strongly suggests one, given that a dual Imfinzi/chemo cohort failed to beat chemo on OS. In 2019 both arms had read out positively versus chemo for the PFS co-primary, but until full numbers are revealed no analysis of the precise effect is possible (Poseidon scores, but tremelimumab’s role is still unclear, October 29, 2019). Poseidon comes after numerous late-stage failures showed tremelimumab to be pharmacologically inert and to have a deleterious effect, likely because of toxicity-related dropouts. Today's surprising success is either validation at last, or simply shows that if you throw enough spaghetti at a wall eventually a piece will stick.