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WCLC 2021 | ZENITH20: poziotinib in EGFR and HER2 Exon 20 mutant NSCLC
Robin Cornelissen, MD, PhD, Erasmus University Medical Center, Rotterdam, The Netherlands, presents updated efficacy data from the Phase II ZENITH20 (NCT03318939) study of poziotinib in patients with non-small cell lung cancer (NSCLC) with EGFR or HER2 exon 20 insertion mutations. Poziotininb is an irreversible tyrosine kinase inhibitor of EGFR and HER2 exon 20 mutations. Results from the cohort of over 200 patients, with a median of 2 prior lines of therapy, demonstrated promising clinical activity with poziotinib. Overall response rates of 14.8% and 27.8% were achieved in the EGFR- and HER2-mutant cohorts, respectively. The benefits seen were consistent regardless of the specific mutation present and prior therapy received. The treatment was well tolerated, and additional enrolment is ongoing. This interview took place during the IASLC World Conference on Lung Cancer (WCLC) virtual meeting 2021.
Transcript
Poziotinib is an oral HER exon 20 insertion TKI, which is currently being studied in a non-small cell lung cancer for EGFR and HER2 exon 20 insertion patients. This is more of a specific group of patients with a poor prognosis. The regular EGFR TKIs that are available at this moment are not effective in this particular mutation. That’s where poziotinib is being studied. So it’s a large international Phase II trial with multiple cohorts, and I presented the results from cohort one and cohort two and those are both previously treated patients...
Poziotinib is an oral HER exon 20 insertion TKI, which is currently being studied in a non-small cell lung cancer for EGFR and HER2 exon 20 insertion patients. This is more of a specific group of patients with a poor prognosis. The regular EGFR TKIs that are available at this moment are not effective in this particular mutation. That’s where poziotinib is being studied. So it’s a large international Phase II trial with multiple cohorts, and I presented the results from cohort one and cohort two and those are both previously treated patients. Cohort one is for EGFR and cohort two for HER2 exon 20 insertions. In both cohorts the tests for these mutations were done locally. Patients received 16 milligrams of poziotinib once a day and primary outcome was overall response rate and the lower bounds of the 95 confidence interval was 17%.
So what we saw in this study group was that for the HER2 cohorts the primary endpoint was met, the response rate was 27.8. Therefore, the primary endpoint was met with a disease control rate of 70%. And most patients in the study shows a tumor size reduction. For cohort one, EGFR exon 20, the primary end point was not met with response rate of 14.8%. And while this primary endpoint was not met still the disease control rate was high with 68% disease control rate, and also a majority of patients showing a tumor size reduction. So still the drug is clinically active in these patients.
We tend to see grade 3 treatment related adverse events in about a quarter of patients, diarrhea and rash. This is one of the things that we’re looking in at this moment to see whether an alternative treatment schedule can cause less side effects and the preliminary data from the fifth cohort that is randomizing different treatment schedules already showed that a bi-daily schedule of 8 milligrams, two times a day causes less side effects, and hopefully the treatment adherence will be higher. So that more patients can tolerate poziotinib better.
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