Phase 3 CLEAR Trial in mRCC

EP: 1.Overview of Renal Cell Carcinoma (RCC)

EP: 2.Classification of Renal Cell Carcinoma

EP: 3.Approaching Treatment for RCC

EP: 4.Goals of Therapy for RCC

EP: 5.Recent Advances in RCC Treatment

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EP: 6.Phase 3 CLEAR Trial in mRCC

EP: 7.Emerging Agents for the Treatment of RCC

EP: 8.Treatment Selection for the Management of RCC

EP: 9.Managing Adverse Events in RCC

EP: 10.Role of Combination Therapy in RCC Management

Thomas E. Hutson, DO, PharmD: What I wanted to share with you all were some of the recent advances in renal cell cancer. There's a couple major clinical trials that have recently been reported at medical conferences, and the hope is that these new therapies that have been reported will find their way to the Food and Drug Administration [FDA] for regulatory approval and will be added to that group of therapies that we choose from for kidney cancer. One of the major recent trials was called the CLEAR study, and just as a point of acknowledgement, I was on the steering committee of that trial and I'm an author of that New England Journal of Medicine paper. The CLEAR study evaluated a combination of immunotherapy/tyrosine kinase inhibitor [IO/TKI]. In this case, it was pembrolizumab and lenvatinib, where we compared that combination versus lenvatinib and everolimus, which is a combination of oral therapy that we utilize in relapsed/refractory metastatic renal cell cancer [RCC].

In other words, we utilize it as the second, third, or fourth therapy versus sunitinib. Thus, it's a three-arm study. Sunitinib is the control arm. As you may recognize sunitinib as a therapy of the past, that therapy, sunitinib, was considered the gold standard therapy up until more recently when we developed checkpoint inhibitors. That [international] study was conducted. To enroll onto that trial, a patient needed to have clear cell RCC, metastatic disease and have received no prior therapy. The patients were randomized to receive one of those three therapies and it was equal randomization. In terms of the endpoints of the study, we were looking at things like progression-free survival, overall survival, tumor shrinkage rate, as well as looking at the safety, looking at side effects and comparing them across the various regimens, and quality of life.

We've reported the final results of this trial of involving over 700 patients at a meeting last year, and the results have subsequently been published. We’ve shown that the lenvatinib/pembrolizumab combination, the IO/TKI combination, produced significant levels of tumor shrinkage; greater than 70% of patients achieving greater than 30% tumor shrinkage. The clinical benefit rate, which means the ability to produce at least stable disease in the patient, was 90%. We saw a complete response rate of 16%, and survival is ongoing right now. Progression-free survival approached 23 months. Thus, this level of activity had not previously been seen in kidney cancer to date, and as a result, there's a lot of excitement about this particular regimen of lenvatinib and pembrolizumab.

I think the proof was already there going into this trial as we already have combinations of IO/TKIs involving axitinib and cabozantinib, but this trial again makes itself unique in its high degree of activity: its high complete response rate, 16%, and a side effect profile, which I really don't have time to go through, but was very tolerable. There were no unusual side effects than what would be anticipated with a combination of a checkpoint inhibitor and an oral therapy, the main ones being fatigue, diarrhea and raising blood pressure.

Thus, we anxiously await regulatory approval of this drug. We must give some caution, however, that anytime we look at the initial results from a clinical trial, we must take a step back and we can certainly celebrate the advance, but we need to confirm with longer follow-up the benefits of the therapy. Then, although it's very exciting to try to compare the results of this regimen versus some of the other regimens we’ve discussed, that also is not something that is generally recommended to do, especially with these early results. Hence, I think the CLEAR study definitely adds now the potential for another regimen, and its unique place where it fits as a therapy for kidney cancer is still yet to be fully decided.

This transcript has been edited for clarity.