Mobocertinib Use in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive mNSCLC - Episode 2

Efficacy Data From the EXCLAIM Cohort in mNSCLC

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Shared insight on efficacy data with mobocertinib from the EXCLAIM cohort of patients with platinum-pretreated EGFR exon 20 insertion–positive mNSCLC.

Transcript:

Gregory Riely, MD, PhD: This is really the meat of the efficacy analysis. These are the response rate data. As with so many of these trials today, there’s an independent review committee [IRC]–assessed response, which is in the green in the upper left. Then there’s an investigator-assessed objective response. For whatever reason, these are a little further off than we often see, so we can maybe focus on the IRC, the independent review committee–assessed response. We see a 32% response rate in the prior platinum cohort and a 24% response rate in the EXCLAIM cohort. Certainly, reasonable response rates; it clearly stands out that it’s not quite what we see with, say, osimertinib in EGFR exon 19 deletion, but certainly better than the standard therapies that we would otherwise have available for our patients. Looking over on the right, one of the end points that the FDA seems to like is this duration of response in confirmed responders. I think if you look at the independent review committee numbers, in the prior platinum cohort, it’s a median of about 17.5 months in those patients who respond. I’ll say, I don’t love the duration of response end point just because it’s not something we can know up front when you meet a patient. When you talk through a treatment with a patient, at least for me, they ask, “How long is this drug going to work for me? How is it going to work for me?”

For me, the number I focus on is the progression-free survival [PFS] because that’s the number that you can take of the patient sitting in front of you, what’s the median time they’re going to be on the drug. From the prior platinum cohort, we see from the independent review committee assessed PFS at 7.3 months at the median. Certainly, some reasonable time on treatment. I have a little harder time interpreting the overall survival data here. The median overall survival was 24 months. I think as Dr Mekhail highlighted, this group of patients had a range of prior therapies, so it’s not as though this is a standard second-line cohort. This is a group of people who had up to 3 prior therapies, so that median overall survival of 24 months is honestly pretty impressive given that prior treatment.

Tarek Mekhail, MD: Greg, I actually like the duration of response end point because when I talk to my patients, and again, I would have loved to see a 90% or higher response rate, but it isn’t the case. What I tell my patients is, “The point of this drug is if it works, it’s going to work well.” Perhaps, we’ll know if it works or not in 6 or 8 weeks. Certainly, we don’t have the high response rate you see with osimertinib and deletion 19, exactly like you said, and that’s unfortunate. But it looks like those in whom the drug works, the median duration of response is 17.5 months, which is very reminiscent of the median duration of response you get with osimertinib when it works. The drug is active in whom it’s going to work, or in whom it’s going to be active. I wanted to comment on that.

Gregory Riely, MD, PhD: I think that’s a good way to put it. I guess I hadn’t thought about framing it that way. It’s a different framing, and I think it’s a very useful one because you’re right, 6 or 8 weeks in, we’re checking a scan, and if we get a sense that the patient’s responding, we can give them the hint that their median time on treatment is significantly longer. That’s great. This is the waterfall plot. Do you want to take us through this figure?

Tarek Mekhail, MD: Yes. I like the visual, and I think there are 2 visuals on that slide. All the bars that are going below the 0, that’s reflective of the disease control rate, I would say. The response rate was around 25%, but the vast majority of patients had tumor shrinkage to some extent. That’s the first visual I see. Going into the treatment, most of the patients wouldn’t have progressed, at least during the first evaluation. That’s the first hand. All these colors, however, are kind of intellectually disappointing because every color represents a variant of the exon 20 insertion, and I would have loved if we discovered in this paper a variant for which the response rate is going to be very high, even at the expense of the other variants. That’s how we choose a drug that has a very high response rate on a particular type of exon 20 insertion. Every color is represented almost equally, so we didn’t get a hint whether mobocertinib is more active in one variant of exon 20 insertion versus another. These are the 2 visuals. I don’t know if you have other comments on that, Greg.

Gregory Riely, MD, PhD: No, I think that’s a great way to describe it, that it’s intellectually disappointing that we couldn’t find the particular variant that benefited. But you’re right, the fact that you see these response rates, which are relatively low, but the vast majority of patients have some tumor shrinkage, which is certainly reassuring that the treatment leads to disease control for most of the patients.

This is a couple of other ways to look at the data. On the left is, I guess we’d commonly call it a swimmer plot, which looks at duration of treatment for a subset of patients on mobocertinib. You see it, again, color-coded by the type of EGFR exon 20 variant, but you see a significant proportion of the patients still on the drug at the completion of the study. On the right are the survival curves that correspond to those 2 end points of duration of response and median overall survival, that median duration of confirmed response of 17.5 months. As a reminder to folks, this is taking people who enroll, and then when they have a confirmed partial response, how long do they maintain that partial response? That’s what that figure in the upper right corner is, the median duration of confirmed response. Then, of course, the median overall survival is, as we often talk about, an important end point to know about, but in this heterogeneous group of patients it is a little hard to really lean on.

Transcript edited for clarity.