Mobocertinib Use in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive mNSCLC - Episode 1

Mobocertinib Use in mNSCLC: EXCLAIM Cohort Study Design


Expert oncologists review data from the EXCLAIM cohort, which analyzed mobocertinib use in platinum-pretreated patients with EGFR exon 20 insertion–positive mNSCLC.


Gregory Riely, MD, PhD: Hello. My name is Dr Greg Riely. I’m a medical oncologist at Memorial Sloan Kettering [Cancer Center, in New York, New York], and I’m happy to be here discussing with a colleague this paper.

Tarek Mekhail, MD: I’m Dr Tarek Mekhail. I work as the medical director of the thoracic program at AdventHealth [Cancer Institute] in Orlando, [Florida,] and I’m happy to be with you, Greg.

Gregory Riely, MD, PhD: We have this opportunity to look through this paper, “Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer.” It’s quite a mouthful. We’ll jump into this, maybe starting with the background here. The first point here I’d raise is that mobocertinib is an oral tyrosine kinase inhibitor [TKI] targeting EGFR exon 20 insertion, maybe even stepping back to remind ourselves that EGFR exon 20 insertion is a pretty uncommon event, it probably happens in about 1% or 2% total of people with non–small cell lung cancer. This is, of course, different than the conventional EGFR sensitizing mutations like exon 19 deletion or exon 21 L858R-type mutations. This is a drug that’s meant to be for this group of patients. Dr Mekhail, do you see patients with this particular mutation from time to time?

Tarek Mekhail, MD: Yes, absolutely. I participated in that clinical trial, and we probably have perhaps a dozen patients with exon 20 insertion, and certainly, this is an uncommon mutation. We typically see this mutation in the same kind of patients we see with the other sensitizing mutations, but if you don’t look for it, you will not find it, and it is quite uncommon. But when you have a trial like that, you tend to see these patients coming to your site.

Gregory Riely, MD, PhD: Definitely. We’ll go through the design of this trial in the next slide. This paper is a combination of a couple of different cohorts in this trial. This is a protocol that started at the very beginning, as you’ll see at the top there, this is a phase 1 dose-escalation 3 + 3 design, so a standard type of phase 1 trial. Then, when it got to a recommended phase 2 dose, you see all these cohorts that were enrolled here, cohort 1, 2, 3, 4, 5, 6, 7. Then they enrolled this EXCLAIM cohort, which is patients who had EGFR exon 20 insertions, you see this in the bottom right, patients who’d had prior treatment. This analysis that we’re looking at here, it mixes cohort 1 and the EXCLAIM cohort together a bit.

I think it’s worth dwelling on this slide for just a moment. Cohort 1 is patients who had EGFR exon 20 insertions who were enrolled in the beginning, and 22 of those patients actually had prior platinum. They’re lumped together in one of the cohorts in the study with the 86 patients in this green group, the EXCLAIM group, who had prior platinum. So it’s important to put this together. But this is ultimately a relatively conventional phase 2 design where everybody got the drug, and then we were able to assess the efficacy by response rate, that sort of thing. Dr Mekhail, do you want to take us through the baseline characteristics in these 2 cohorts?

Tarek Mekhail, MD: Yes, concerning these 2 cohorts, we have the PPP, or prior platinum-treated patients, which is 114 patients, and the EXCLAIM cohort. Ten patients in the EXCLAIM cohort did not have prior platinum, but the rest, which are 86 patients, are included in the prior platinum cohort, so you’ll find similarity in the results that we’re going to talk about. This is almost an artificial division just because EXCLAIM had some patients who did not previously receive platinum. That, again, emphasizes exactly what I said. It’s the typical patients you see sensitizing mutations in, patients are a little younger than the usual, the median age is around 60. We tend to have more females, but certainly an abundance of males as well, 34% males roughly in both cohorts. Asians, Black, White, so really the whole geographic areas were well represented, as well as some different ethnicities. The vast majority are adenocarcinomas. There is 1 squamous cell carcinoma; whether that’s a real squamous cell carcinoma, we can argue about it. One patient had large cell carcinoma. Again, phenotype is not a genotype, so thinking about females, never smokers, yes, there is an abundance of patients on these, but certainly, there are males and there are smokers. You see here on the table on the right, former smokers, 27% and 25%, respectively, on the prior platinum and the EXCLAIM cohort. I think this is important to recognize.

The vast majority, obviously, the 114 patients on prior platinum had prior therapy, but there are patients who had 2 regimens, and there are patients who had more than 3 regimens, so some patients are in a heavily pretreated population. On the PPP cohort, 100% received platinum-based therapy before. On the EXCLAIM cohort, 10 patients didn’t, so it’s really 90%. There was immunotherapy on both arms. Many patients had been treated with immunotherapy in the past, 40% roughly. Other TKIs, this is important to recognize, some patients were previously treated with different TKIs. An important point is that a third of patients previously had brain metastases. All patients had to have treated brain metastases to be included in the study. I think that’s something, as we read the paper, we learn a little bit about CNS [central nervous system] importance and perhaps activity or lack of for mobocertinib in patients with CNS disease.

Gregory Riely, MD, PhD: Thank you for taking us through that. Just to emphasize your point too, that while we see a significant proportion of the patients were never smokers, 2% of the patients were current smokers, and so we’ve got to test to find these mutations in all of our patients.

Transcript edited for clarity.