AZ's immunotherapy combo misses the mark in untreated lung cancer

AstraZeneca’s immunotherapy combination has missed the mark in certain patients with untreated lung cancer, failing to improve survival compared with standard chemotherapy in a phase 3 trial.

In the NEPTUNE trial Imfinzi (durvalumab) and tremelimumab – a combination of a PD-L1 and a CTLA-4 immunotherapy – could not outperform standard platinum-based chemotherapy in previously-untreated Stage IV (metastatic) non-small cell lung cancer.

The trial was performed in an all-comers population with the primary analysis involving those patients with a high tumour mutation burden (TMB).

TMB measures the number of mutations within the genome of a tumour, and tumours with high levels of mutations may be more visible to the immune system.

AZ did not give detailed trial results – they will be announced at a forthcoming medical conference – but said the topline readout was negative, with the combination failing to meet its overall survival endpoint compared with chemotherapy.

Safety and tolerability findings were in line with previous trials involving the combination.

Many cancer immunotherapy manufacturers are finding first line lung cancer a tough not to crack, although Merck & Co has managed to get its Keytruda (pembrolizumab) approved in this highly lucrative use.

Imfinzi has a somewhat chequered history in trials – it missed the mark in the phase 3 MYSTIC trial in untreated lung cancer, which AZ hoped would allow it to take market share from Keytruda in this indication.

But despite this setback other trials have been more successful, allowing for an initial FDA approval in bladder cancer in 2017, followed by another indication in some patients in the earlier stages of lung cancer.

This has allowed Imfinzi to produce blockbuster-level sales, with sales of $633 million in the first half of this year alone.

Imfinzi is also being tested as monotherapy in the phase 3 PEARL trial, and in combination with chemotherapy with or without tremelimumab in the phase 3 POSEIDON trial as part of an extensive late-stage immuno-oncology programme in Stage IV NSCLC.