It's another fail for AstraZeneca's I-O combo, but it may not mean what you think

Investors shouldn't read too much into Imfinzi and tremelimumab's failure in third-line lung cancer, analyst Tim Anderson contends. (AstraZeneca)

AstraZeneca has come up short in another lung cancer trial of its immuno-oncology combo, this time in patients who've failed on two prior treatments.

But investors shouldn’t use the outcome to predict the forthcoming results of a closely watched first-line study, analysts say.

Tuesday, the British drugmaker said its PD-L1 med Imfinzi and candidate tremelimumab had failed to improve survival in third-line patients whose tumors didn’t express PD-L1. There was a bright spot, though: A substudy that pitted solo Imfinzi against chemo in PD-L1-positive patients showed a “clinically meaningful” difference for the AZ drug in the risk of death.


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The results weren’t terribly surprising to analysts; Bernstein’s Tim Anderson, for one, said in a note to clients that he thought the trial, dubbed Arctic, “was likely to yield mixed results (and it did).”

And the way he sees it, that’s not such a bad thing. Overall, “the field has moved on,” he said, calling Arctic “basically the hangover from a now abandoned hypothesis” that PD-L1/CTLA4 pairings such as AZ’s will extend benefits to the PD-L1 negative population.

ODDO BHF’s Pierre Corby wrote in his own note to clients that removing the combination from models would have “minimum impact.”

RELATED: AstraZeneca's Mystic shortfall is an immuno-oncology shake-up for Bristol-Myers and a bolster for Merck and Roche

And while investors may be tempted to take the outcome as a sign that the Imfinzi-tremelimumab combo is destined for failure in first-line, PD-L1-positive patients—the all-important population in the I-O market—they shouldn’t, Anderson said.

“That outcome is certainly not foreshadowed” by the miss in PD-L1 negative patients, he wrote.

If there’s any readthrough to Mystic, AstraZeneca’s first-line trial, it’s that Imfinzi still holds promise as a monotherapy, Anderson figures.

“We continue to believe that Imfinzi is likely is show an OS benefit in 1L PD-L1(+) patients, and obtain a (modest) foothold in the market,” he wrote.

RELATED: 2018 is here. Now get ready for ‘market-defining’ I-O readouts

Of course, it’ll still be a while before industry watchers have that data, which is slated to arrive in the second half of the year. And in the meantime, there will be plenty of other key I-O news from companies including Merck and Roche that should keep investors busy.

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