Xiuning Le, MD, PhD, MD Anderson Cancer Center, discusses results of cohort 5 from the ZENITH20 clinical trial, which revealed that twice daily poziotinib dosing improved the adverse event (AE) profile of the treatment and retained anti-tumour activity in patients with non-small-cell lung cancer (NSCLC) with EGFR or HER2 exon 20 mutations. These data were presented at the 2021 AACR Annual Meeting.

Transcript

My name is Xiuning Le. I am a thoracic medical oncologist at MD Anderson Cancer Center here in Houston, Texas. I am a clinical investigator. I work on many clinical trials, especially with a focus on targeted therapy, especially the novel therapy for non-small cell lung cancer patients.

Here, I want to talk about one of our recent publications at AACR talking about cohort 5 of the ZENITH20 clinical trial, where poziotinib, the medication and small molecule inhibitor, was evaluated in non-small cell lung cancer patients whose tumor have either EGFR or HER2 exon 20.

ZENITH20 trial has been ongoing for a number of years. ZENITH20 for now has 7 different cohorts evaluating patients of different molecular makeup and then patient of different need in different clinical stages.

Cohort 2 was targeting HER2 non-small lung cancer patients, where we find good efficacy in this cohort of patients where the response is around 28%. Then we have also a pretty good duration of response.

Together with that good results, we also find out that the poziotinib has the toxicities that can compromise a patient's quality of life. Some of the toxicities are so-called on-target toxicity, where, because a drug is targeting EGFR or HER2, which can be normally expressed on some of our normal tissue as well...

So when the poziotinib, when the drug, is engaged in the target, the good thing is to shrink the tumor, however also engage the target in the normal part of the body, inducing side effects. The big ones are rash and diarrhea.

Of course, the mucositis basically is a rash inside the mouth. Also, it is a challenge for this patient population. The cohort 5, really focusing on evaluating how can we improve the side effects. One approach we are taking here is, instead of doing a full dose every day, we are splitting the same dose.

We are splitting the same dose into two doses, given twice a day. The total dose every day is still the same for each patient, so the total dose is not compromised, where the regimen is different, the schedule is different, so that the patient is taking a lower dose twice a day.

The idea is that, by doing a lower dose twice a day, we can have the peak level in the patient blood of the drug to be decreased so that the toxicity can be decreased. However, the total dose, and then sometimes we use a word, area under the curve, is now changed. We are looking forward to see if we can preserve the efficacy component of it.

This abstract, we reported our first small groups of evaluation on the splitting dose. Really, as expected, the toxicity, especially the grade-3 toxicity that is associated with this EGFR inhibitor, including rash and diarrhea, significantly decreased by doing the splitting dose.

When we compared the group of patients who are taking 16 milligrams every day, which is the original scheduled dose, versus 8 milligrams -- half, twice a day -- the 8 milligrams, twice a day group patients had a lot less rash and diarrhea.

Then the first time the group of patients needed a dose delay or dose reduction is also much, much later, compared to the 16 milligrams, twice a day. From different parameters, I think we show here that 8 milligrams, twice a day is better tolerated.

We also had enough evaluation to give us a preliminary efficacy signal to tell us the other side of the story. Well, you decreased the toxicity, but can you still preserve your efficacy? Especially in the 8 milligrams, twice a day group patients, here, we saw that the response is actually better than the 16 milligrams daily patient group.

The numbers are very small. We were able to look at the first 19 patients in each group, but the result is very encouraging, although preliminary. It is consistent with our hypothesis going into the cohort. What we said is the total dose is still the same, so we do not expect to compromise the efficacy.

In addition, by decreasing the toxicity, we also think it is possible that more patients can take on the regular dose. Therefore, actually, the anti-cancer efficacy can either actually be improved by using the twice a day approach.

With this very preliminary data, with these preliminary results, showing that twice a day, 8 milligrams dose can help with decreased toxicity, and in the meantime, preserve or maybe enhance efficacy, I think the cohort 5 has been conducted in a pretty successful manner.

For us going forward, we are going to enroll more patients into the 8 milligrams, twice-daily group to further evaluate if that truly shows a benefit that truly can mitigate a lot of the side effects and toxicity. We are still open and enrolling, and in the meantime, we are looking forward to future data, future report, to see if this approach will work in a bigger patient population.