Imvigor011 is a randomised phase III study, it’s a study in urothelial cancer. It’s adjuvant, so it’s post-surgery with patients who have been cured by surgery, effectively, but we know many of those patients relapse. If we do a blood test, circulating tumour DNA, 40% of patients at that time are positive and those patients that are positive almost all of them go on to relapse. So what we’ve done is we’ve done a randomised phase III where we enriched into that population, focussing on those at risk, randomised to atezolizumab versus placebo. We’ve also at the same time tracked those patients that are ctDNA negative and if they’re negative and they become positive they’re also randomised to atezolizumab or placebo. There’s a third population that’s negative that remains negative and we work out what happens to them to make sure they don’t come into harm’s way.

So it’s a big randomised trial, three stages: the screening phase, which I’ve talked about now and we screen patients for ctDNA for a year. They had to enrol in the trial within 26 weeks of cystectomy, they could have had previous neoadjuvant chemotherapy if they wanted to, and they’re essentially then going through serial ctDNA testing. If they become positive at any time randomised to atezolizumab versus placebo. The primary endpoint is progression free survival.

We randomised 250 patients, a 2:1 randomisation, and essentially what we showed was a significant delay in disease free survival, a hazard ratio of 0.64. We also showed in that curve that if you were ctDNA positive almost all of the placebo patients went on to relapse.

The second thing we showed was significant benefit in overall survival with a hazard ratio of 0.59, curves going apart and staying apart nicely in this really high risk population. We showed that atezolizumab was associated with a ctDNA clearance in about 25% of patients, underpinning the biology. We showed atezolizumab had a predictable adverse event profile – we know a lot about that already. It’s a year, only a year, of adjuvant therapy as is standard.

We also tracked that negative population that remained negative and we showed that they had a really good outcome. They don’t seem to be in a significant harm’s way associated with dying of urothelial cancer. Remember, this is a population with a median age of 70 years old so it’s a population where we feel overall at this point, with the results of this trial and the results of the previous trial, IMvigor010, where we showed a very similar thing in the exploratory analysis. In that trial we also showed ctDNA positive patients who received atezolizumab versus best supportive care had a significant reduction in the risk of death. We also showed in those ctDNA negative patients they had a good outcome and atezolizumab didn’t help.

So this is the prospective study to confirm those findings. I think it does underpin this as a biomarker that we can use post-cystectomy to decide which patients should start immune checkpoint inhibition, specifically atezolizumab.