Michael R. Migden, MD:When the phase I trial of cemiplimab was underway for advanced cancers of multiple tumor types, it was noted that a patient with advanced cutaneous squamous cell carcinoma had a durable complete response. This led to the development of expansion cohorts, 7 and 8, and that was for 1 group of patients; a combination of locally advanced and locoregional metastasis. The other group was distant metastasis because of the good objective response rate and tolerability. Based on those expansion cohorts, this led to the development of the pivotal registration phase II study, looking at just cutaneous squamous cell carcinoma.
Based on the data from the expansion cohort 7 and 8 from the phase I study in CSCC, as well as the preliminary data from the pivotal registration phase II trial of cemiplimab, this therapy was granted breakthrough therapy status by the FDA. This led to fast tracking of its evaluation and now to its approval.
In the phase II pivotal registration study that looked at both metastatic, as well as locally advanced patients, we saw good results, both in terms of depth of response rate. It’s particularly notable that patients with locally advanced disease are very easy to document, and easy to biopsy because of the location of the disease being more visually and clinically amenable to assessment. So, when people have a complete response, a dramatic response, and you have an externally visible lesion, there’s potential for more clear-cut assessment of that response. The tissue is easy to reach for multiple biopsies to prove that what you’ve seen is actually a complete response.
I had some patients who said that their tumors melted away or broke off, and what was left of them fell off onto the floor. So, these are things that often start happening early in their therapy. And one of the first things people report after sometimes only a few infusions, is a significant decrease in pain. Once you start seeing that response, it can proceed rapidly. I have multiple patients in the study that have a complete response, and some of them have come off therapy, and their complete response persists without any evidence of disease recurrence. Of course, there’s a spectrum of responses. Some people have more partial response or stable disease. There’s always the possibility that you’ll have a patient who doesn’t respond or who progresses. In my patients that I enrolled into the study though, the vast majority of patients had a response.
Also, when you look at metastatic disease, we have to ask where the patient came from, what was the prior state of the patient that led to their metastatic disease. And, from my perspective, the vast majority of metastatic patients start with some form of locally advanced disease. These are cases where there’s been some surgery, maybe it didn’t get all the tumor and it recurredyou can think of this as a continuum. So, if that’s the way the natural history of their disease progressed, if you can intervene at an earlier stage when they’re still locally advanced, you might have a disease that’s more treatable, that has a higher response rate, and that’s the way I think about it.
It’s really important when you’re looking at patients that have locally advanced disease, not to let them go, because if you let them go, they go on to metastatic disease and the more distant the metastasis, the belief is that the more difficult the disease is to treat, especially when you’re looking to try and get a lasting complete response. Definitely, from my perspective, metastatic disease and distant metastasis within that group, is a much tougher disease to get to that complete response end point.
Transcript edited for clarity.