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.

Selected pivotal studies containing tremelimumab
Trial Cancer type Treatment cohort(s) Enrolment Result/data due
Arctic 3rd-line NSCLC Imfinzi +/- tremelimumab 597 Fail
Eagle 2nd-line head & neck Imfinzi +/- tremelimumab 736 Fail
Mystic 1st-line NSCLC Imfinzi +/- tremelimumab 1,118 Fail
Poseidon 1st-line NSCLC Imfinzi + chemo +/- tremelimumab 1,000 Tremelimumab combo arm positive for OS; Imfinzi arm negative for OS (both positive for PFS)
Neptune TMB-high, 1st-line NSCLC Imfinzi + tremelimumab 953 Fail
Danube 1st-line urothelial Imfinzi +/- tremelimumab 1,126 Fail
Caspian 1st-line SCLC Imfinzi + chemo +/- tremelimumab 988 Imfinzi arm positive for OS, tremelimumab combo arm negative for OS
Kestrel 1st-line head & neck Imfinzi +/- tremelimumab 823 Fail
Himalaya 1st-line hepatocellular Imfinzi + tremelimumab 1,324 H2 2021
Adriatic SCLC maintenance Imfinzi +/- tremelimumab 600 2022
Strong Various Imfinzi +/- tremelimumab 1,200 (up from 869) 2022 or beyond
Nile 1st-line urothelial Imfinzi + chemo +/- tremelimumab 1,215 (up from 885) 2022 or beyond
Source: & EvaluatePharma.

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