Poseidon scores, but tremelimumab’s role is still unclear

After Bristol-Myers Squibb’s Checkmate-9LA surprisingly read out positively last week, a win for Astrazeneca’s similar trial, Poseidon, might have been easier to call. Indeed, yesterday Astra toplined Poseidon as positive – for now only for progression-free survival. Both trials, in first-line NSCLC, added chemo on top of an anti-PD-1/CTLA-4 doublet, which in Bristol’s case was Opdivo/Yervoy and in Astra’s Imfinzi/tremelimumab. However, still unanswered is one key question: what exactly does CTLA-4 inhibition bring to the party? This must be quantified to ascertain whether Merck & Co’s dominant Keytruda/chemo combo can be challenged. While ‘9LA tested only the PD-1/CTLA-4/chemo triplet versus chemo, Poseidon gave Imfinzi plus chemo alone in one cohort, and Imfinzi/treme/chemo in another. Yesterday Astra said both had beaten chemo alone in PFS terms, but it is only when full data are revealed that a numerical comparison between the doublet and triplet can be made. Merck today said its own Keynote-598 trial, comparing Keytruda plus Yervoy to Keytruda alone, “will provide, we hope, definitive information”. For its part, Astra said it would file based on PFS alone, and clarified that an OS readout from Poseidon should be available next year, not in 2021, as it had stated last week.

Selected first-line NSCLC studies
Trial Company Active cohorts Primary endpoints Secondary endpoints
Checkmate-9LA Bristol-Myers Squibb Opdivo + Yervoy + chemo OS vs chemo alone, toplined positive Include PFS
Poseidon Astrazeneca Imfinzi + chemo +/- tremelimumab PFS of doublet vs chemo, toplined positive
OS (data expected in 2020)
PFS of triplet vs chemo, toplined positive
Keynote-598 Merck & Co Keytruda + Yervoy (PD-L1≥50%) OS & PFS vs Keytruda alone (completion 2023) Various

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