Here at ASCO 2017 we’re presenting the updated data on bladder cancer, metastatic urothelial carcinoma, using avelumab and we have a pooled analysis of two cohorts. One is a 44 patient cohort, the other one is a 200 patient cohort so we have a combined group of patients of 250 patients. We have data on 161 patients where we have at least six month follow-up and we see very nice responses. So we have an overall response rate of 17.4% and one of the exciting things about this is that at the time of data cut-off 82% of the patients were still responding.
17% of the whole 250?
Of the 161, so the patients that have at least six months follow-up.
Can you tell us more about how you got to avelumab as an indication in this scenario because with the recent approvals for Merkel cell carcinoma was that in the works beforehand or afterwards?
It was in the works at the same time. Avelumab has been clinically developed at the NCI so on May 9th of this year, 2017, the FDA actually approved avelumab for the treatment of metastatic urothelial carcinoma based on our pooled analysis that we have.
From the Merkel cell results there was at least one serious event. Have you had the same kind of results for bladder cancer?
Yes, in terms of adverse events about two-thirds of the patients experienced an adverse event and about 13% of the patients had an immune related toxicity. In terms of grade 3 or higher adverse events it was smaller, only about 3% of patients, 2.4% of patients had grade 3 or greater immune related toxicity. There was one death due to pneumonitis from the treatment.
Looking at the balance of 17% complete response and 13% immune adverse response it seems like that’s quite a high risk for will you be in the sixth of patients who respond or the sixth of patients who get these serious events. Are there any ways that you could mitigate this with either combination therapies?
That’s a great question, I don’t think we know the answer to that yet. It would be great if we could know which patients are going to have immune related toxicities. The majority of the immune related toxicities are mild, they’re grade 1, grade 2, they’re skin rashes or elevation of liver enzymes or pancreatic enzymes. So it’s nothing major clinically to the patient. Really the severe immune related toxicities are less common, they’re usually in the range of 5-8%.
Speaking of predicting that response there, were the complete responses due to any PD-1 expression?
That’s a great question. We actually did look at the PD-L1 expression in the patients with metastatic urothelial carcinoma treated with avelumab and we did see a higher response rate for the patients that were PD-L1 positive, 25% versus 13% for the PD-L1 negative patients. This wasn’t statistically significant but there was a trend towards an improvement.
The recent approval, is that as first line, second line?
The recent approval of avelumab for metastatic urothelial carcinoma is for the second line treatment, patients that are refractory to standard chemotherapy.
What are the plans for taking these trials forwards to either new cohorts or expanding into different staging?
One of the things that we’re doing now is moving these agents to earlier states of disease such as the first line setting, the maintenance setting or even in earlier states of bladder cancer like muscle invasive and non-muscle invasive. Also trying combination therapy to see if we can improve upon the response rates that we’re seeing right now.