Transcript:Thomas Powles, MBBS, MRCP, MD: Durvalumab is a PD-L1 inhibitor. It’s a drug that has been developed in bladder cancer over the past 2 years. 1108 is the pivotal trial to achieve FDA approval. It’s essentially a very, very large phase I trial, as we’ve seen before with other drugs in this area, where there is a fixed dosage established and the dose is then given to an expanded cohort of patients. These patients have urothelial cancer or bladder cancer, and the trial showed very quickly activity, as we’ve seen with other drugs previously. And for that reason, the cohort expanded.

The trial initially looked to individuals who only overexpressed the PD-L1 biomarker. The companion diagnostic with this drug is the SP263 biomarker. Each immune checkpoint inhibitor has its own individual biomarker, so that has complicated the field with 5 biomarker programs. But this biomarker in the initial parts of the analysis during the exploratory phase showed really promising data with very high response rates and quite high sensitivity and specificity. And for that reason, the cohort expanded to test the negative population as well. And the last part of the trial, therefore, is we then looked to essentially all-comers and then retested the biomarker to see how active it was as a test in the validation phase.

When you look at a population now—which we just published very recently and that has been accepted for publication in JAMA Oncology—when you look at the cohort that we’ve tested and we got accurate efficacy data on now over 100 patients, the degree of selection in that, if you look at the response rate in the biomarker positive population, is in the region of 30%, 20% in the all-comer population, and that looks very competitive compared to other agents. The drug is really well tolerated and the responses are long-term and durable. I’m always nervous about talking about overall survival in phase I trials because there’s a lot of patient selection. But if you look at the overall survival of this cohort compared to historical controls, it’s longer than you would expect, and we clearly hope that’s going to translate into a survival signal in the randomized study.

There are issues around drug delivery, so this was given on a 2-weekly schedule. In some of the subsequent studies, it has been given on a 4-weekly schedule. Durvalumab has been approved by the FDA in the past 2 months. Durvalumab is a drug that has been approved in individuals who’ve previously failed platinum-based therapy. That’s very similar to the approval of other agents in this setting. The biomarker is something that is being developed, but is not a crucial part of the approval, so it’s an all-comer’s type approval. We’ve used a lot of durvalumab in our center. We probably have treated 20 patients with durvalumab now. And what we’re seeing is a well-tolerated drug, we’re seeing a drug that patients are receiving. We’ve had long-term durable responses, as you would expect. We’ve had patients who progressed through the drug as well. So, it’s very much in line with what we would expect to see and similar to what we’ve seen with other agents.

And it’s not until we look at the randomized trials that we will be able to determine whether or not there’s any difference between these agents, which is why studies like durvalumab in the frontline setting—testing single-agent durvalumab and durvalumab and tremelimumab together versus all-comers chemotherapy in over 1000 patients—will potentially change the way we see disease in the future.

Transcript Edited for Clarity