AZ’s immunotherapy combo fails again in lung cancer

AstraZeneca had placed its immunotherapy Imfinzi (durvalumab) at the centre of its efforts to rebuild its sales – but after a shock failure last year in first line lung cancer, the drug has also come up short in previously treated patients.

Developed by its MedImmune biologics unit, AstraZeneca was testing Imfinzi in the phase 3 ARCTIC trial as a combination with its other immunotherapy tremelimumab.

Imfinzi is an PD-L1 inhibitor drug, and the companies hoped that combining it with the CTLA-4 class tremelimumab, there would be stronger effect against cancer.

Faced with an ageing portfolio of approved drugs, AZ had placed Imfinzi at the centre of its efforts to boost sales to $40 billion by 2023

But the phase 3 ARCTIC trial, in patients with locally advanced or metastatic non-small cell lung cancer with low or negative PD-L1 levels who have received at least two prior treatments, the combination therapy did not significantly or clinically improve progression free survival.

In a sub-study assessing Imfinzi monotherapy there was clinically meaningful reduction in the risk of death compared with chemotherapy, but the study was not powered to show statistical significance.

The results caused shares in AZ to tick down as investors mulled over another perplexing failure from a drug the firm had hoped would compete with blockbuster immunotherapies such as Merck & Co’s Keytruda (pembrolizumab), and Bristol-Myer Squibb’s Opdivo (nivolumab).

In July last year the durvalumab+tremelimumab combination came up short in the MYSTIC first-line lung cancer trial when an early readout showed it failed to improve progression-free survival in patients whose tumours express PD-L1 on 25% or more of their cells.

AZ is continuing with MYSTIC to see if either the Imfinzi monotherapy, or the combination, can improve overall survival in first line lung cancer, with results due later this year

But Deutsche Bank analyst Richard Parkes told Reuters the expectations for this "should now be very low".

Sean Bohen, AZ’s chief medical officer, said: "While we are disappointed that the combination of Imfinzi plus tremelimumab did not result in a statistically-significant survival benefit in this heavily pre-treated patient population, we are encouraged by the activity of Imfinzi monotherapy observed in this trial and look forward to presenting the full data from the ARCTIC trial at an upcoming medical meeting."

Imfinzi has been approved as monotherapy for stage 3 lung cancer patients with inoperable tumours, and in advanced bladder cancer.

Full data from ARCTIC will be presented at a forthcoming medical meeting

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