Medicine Matters oncology

Hi, I'm Dr. Chung-Han Lee. I'm at Memorial Sloan Kettering Cancer Center. And today, I had the opportunity to present Hope 111, or also known as KEYNOTE-146, which was a phase 2, open-label, multicenter study of lenvatinib in combination with pembrolizumab in patients who had previously progressed on an immune checkpoint inhibitor.

So this study was really the first prospective study of a TKI/I-O combination in patients who had previously progressed on an immune checkpoint inhibitor within RCC. So the combination of lenvatinib plus pembrolizumab has been previously studied in immune checkpoint inhibitor-naive patients. And we actually demonstrated a fairly good objective response rate of about 70%, with a median progression-free survival of 20 months.

So the study that we just recently presented at ASCO were the results of this combination in 104 patients who had previously progressed on an immune checkpoint inhibitor. And what we were really able to demonstrate is, even in the setting of being immune checkpoint inhibitor refractory, we still saw a high objective response rate of 55% by irRECIST and 52% irRECIST 1.1. The median duration of response for the patients who had achieved an objective response was 12 months, with most of the patients who achieved an objective response still remaining on therapy.

So we expect that with longer follow-up, we may see this number increase over time. The median progression-free survival was 11.7 months, with 45% of patients remaining progression free at 12 months. We also did a little bit of subgroup analysis looking at patients who had previously progressed on a VEGF-targeted therapy and patients who had previously progressed on combined immunotherapy, such as the combination of nivo/ipi. And we also continued to show high objective response rates.

From this study, in particular, we would want to see longer-term follow-up to see what those results may be and the durability of that response. We are also curious to see, somewhere down the line, whether or not-- coming off therapy, whether or not patients are able to maintain these responses.

The other aspect that we have to think about is even though these response rates that we're seeing right now are quite high, we are always looking at either biomarkers that help stratify patients into groups that respond better, and selecting out patients who may not necessarily respond, but also looking at alternate pathways that also would benefit from modification and modulation to improve upon the clinical outcomes.

So for right now-- so the combination of lenvatinib plus pembrolizumab is not yet FDA-approved for RCC. It is FDA-approved in drugs like-- cancers such as endometrial cancer. There is a pending registrational phase 3 study looking at this combination in treatment-naive patients. So we really do hope that taking this data as a whole, in conjunction with, hopefully, the readout of the phase 3 being positive, that we'll be able to get this combination in the hands of physicians and to help patients soon.

The main thing that people often ask right now is-- based off of this study, is how does this compare to single-agent TKI? Right now, we really have very little prospective data looking at the results of single-agent TKIs after progression after immune checkpoint inhibitor. However, there is a lot of retrospective analysis that have been done in comparison to those studies.

And certainly, there are many, many limitations that come when we make these types of comparisons. This type of combination does seem to be more active and certainly very hypothesis generating about what type of interaction is happening between the TKI, such as lenvatinib, in combination with the anti PD-1 inhibitor, in this case pembrolizumab.