AstraZeneca's tremelimumab records another miss as Imfinzi combo strikes out in small cell lung cancer

Here’s a sentence AstraZeneca investors are all too familiar with: A combination of checkpoint med Imfinzi and investigational drug tremelimumab missed its primary endpoint in a phase 3 trial. This time, it applies to small cell lung cancer (SCLC).

The immuno-oncology combo failed to show it could extend the lives of previously untreated extensive-stage SCLC patients, AstraZeneca said Tuesday. About 15% of all lung cancer cases are small cell, a fast-growing form of the disease.

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AstraZeneca isn’t all out of luck in that arena, though; on the contrary, it’s currently awaiting an FDA approval for its combination of Imfinzi and chemo, which showed last year that it could cut newly diagnosed patients’ risk of death by 27% compared with solo chemo. In December, regulators gave the combo priority review status, moving up their decision timeline to the first quarter of this year.

In a Tuesday note to clients, SVB Leerink analyst Andrew Berens said he expects AstraZeneca's peak revenues in SCLC, on a risk-adjusted basis, to hit about $413 million in the U.S. and about $828 million worldwide.

AZ, though, had been looking for a leg up on competitor Roche, the only company with an immuno-oncology-based SCLC regimen on the market. Imfinzi plus tremelimumab would have represented a chemo-free option for patients, the British drugmaker figured, differentiating it from Roche’s Tecentriq-chemo pairing.

Unfortunately for AstraZeneca, it has repeatedly struck out with tremelimumab, both in lung cancer and outside of it.

RELATED: AstraZeneca mines for positives in Imfinzi's failed Mystic lung cancer trial

Most notably, the Imfinzi-tremelimumab combo came up short in the all-important Mystic trial a couple of years back, keeping AZ out of a non-small cell lung cancer (NSCLC) market considered by analysts to be immuno-oncology’s most lucrative. But it’s also failed in a host of other arenas, including bladder cancer, where it came up short earlier this month.

So far, chemo combos have in general seemed to fare better in lung cancer than PD-1/L1-plus-CTLA-4 cocktails such as AstraZeneca’s. Just ask Merck, whose Keytruda has run away with the NSCLC market; Roche, which has also found success with the strategy; and Bristol Myers Squibb, which is still struggling to win approvals for its Opdivo-Yervoy duo.

But BMS has also shown repeatedly that adding CTLA-4 drug Yervoy to Opdivo works in other tumor types, from melanoma to liver cancer, leaving some industry watchers to wonder whether the problem is tremelimumab itself.