I have presented the LATIFY study. It’s a randomised study, open label, that compares a new regimen – a combination of an ATR inhibitor, ceralasertib, and durvalumab to docetaxel, the standard of care. Obviously we are in the situation where patients had advanced non-small cell lung cancer without actionable genomic alteration and pre-treated with chemotherapy and immunotherapy. We are, let’s say, in second line.

In this study we have assessed the combination of an ATR inhibitor plus durvalumab because we ran a previous phase II study called HUDSON and we saw that this combination could have an impact on the control of the disease, in particular because this ATR inhibitor modified the microenvironment of the tumours.

So the LATIFY study has a primary endpoint that is overall survival. It was stratified by PS-status, region and also the type of resistance to the primary immunotherapy – if the patient stayed less than 16 weeks they were considered primary resistant. So randomisation was balanced to that. We have also analysed PFS and OS based on key subgroups, in particular where ATM was absent, or we call them ATM-deficient by immunohistochemistry, or mutated, so an ATM alteration.

Basically the trial did not meet the primary endpoint, the overall survival is similar between the two arms – 11.1 months for durvalumab plus ceralasertib and 10 months for docetaxel with a hazard ratio of 0.9. The PFS is the same – 4.1 months in the two arms. If we look at the subgroup with the biomarker, in the ATM-deficient by immunohistochemistry we see a slight improvement of the OS, not the PFS, but it’s a very small subgroup with a wide confidence interval so the data should be interpreted with caution.

One of the striking results of the study is that 7.7% of the patients responded to ceralasertib plus durvalumab, they had an objective response. In this population the duration of response was almost 17 months. So I would say, to conclude, that overall it’s a negative study. In an all-comer population ceralasertib plus durvalumab is not superior to docetaxel for overall survival, PFS and overall response rate. But the 7.7% of patients that respond to this combination, ceralasertib plus durvalumab, had an amazing long duration of treatment – almost 17 months – with a very decent toxicity profile.

What’s next for this study?

The next steps would be to analyse different biomarkers to identify who are the 7.7% of the patients that really benefit from the combination. We are living in an era of precision medicine in lung cancer so getting the good biomarker for the matched drug is something that is obvious. So the next step is to look at what is a good biomarker.