This year what I’m presenting at ESMO is a phase Ib/II clinical trial of lenvatinib plus pembrolizumab in patients with metastatic and advanced renal cell carcinoma.
Can you give us some of the background to that? What is the current treatment regimen?
As of right now, at least in the United States, there are ten FDA approved regimens for the treatment of metastatic renal cell carcinoma. Most of the regimens have been used as monotherapy with the exception of the combination of lenvatinib plus everolimus. The clinical trial that we talk about today is a combination therapy of an immune checkpoint inhibitor in combination with lenvatinib.
And how is this panning out?
The results of the clinical trial were quite impressive. The primary endpoint for this clinical trial was the objective response rate at 24 weeks. With this clinical trial if we look at the total cohort, which included both patients that were treatment naïve and patients that were previously treated, we saw an objective response rate of approximately 63%. Now, if we look only at patients that were treatment naïve we saw an objective response rate of 83% and with the previously treated patients a response rate of 50%. Based off of the time of follow-up at this time the median progression free survival still had not been reached and with further follow-up we may end up knowing those results.
What was it about the combination of lenvatinib and pembrolizumab, as opposed to pembrolizumab with any of the other ten approved regimens?
When we think about use of different tyrosine kinase inhibitors they are largely thought of as VEGF targeted therapies but they also have other effects looking at other tyrosine kinases that they may affect. So lenvatinib is actually also a multi-tyrosine kinase inhibitor, mainly targeting VEGFR1, 2 and 3 and also FGFR1, 2 and 3. When lenvatinib was approved it was approved after treatment with progression on a prior VEGF-targeted therapy, mainly with the rationale of thinking that targeting the FGF signalling pathway would lead to improved clinical responses.
In terms of tolerance have there been any side effects because pembrolizumab comes with a certain raft of side effects that are well known?
In this combination clinical trial, as with all combination clinical trials, the issue of tolerability is certainly an important question. What we have seen, at least with this trial, is although the numbers are still quite small, the toxicities that we’ve experienced are quite similar between those that have received monotherapies. The most common side effects related to this regimen are those that are similar to single agent lenvatinib where the most common toxicity was an elevation in blood pressure.
Then when can we expect to start seeing the median PFS and maybe even overall survival data coming out?
The data cut-off for this clinical trial was March of this year and our hope is that within the next few months with further follow-up we’ll start getting additional PFS information. At this time we still don’t quite know when the data will necessarily mature. The longer it takes essentially will reflect the durability of these responses because we have not yet reached the point at which half the patients have progressed on treatment.
That seems like it covers a lot of the aspects for everything that would be coming out so far. Is there anything that we’ve not mentioned?
No, I think that we’ve pretty essentially covered it. Right now there’s an on-going phase III clinical trial with this combination. For the phase III clinical trial it’s three specific arms, the first arm being lenvatinib plus pembrolizumab, the second arm being lenvatinib plus everolimus and the third arm being standard of care which would be sunitinib at this time.
Isn’t having the phase III out before this trial is completed jumping the gun a little?
It was one of those things in which, based off of our initial prelim analysis, it seemed quite promising and therefore led to the phase III.