Poziotinib Shows Meaningful Activity in EGFR Exon 20–Mutant NSCLC

Adrian Sacher, MD

Poziotinib, when given at a daily dose of 16 mg, was found to demonstrate clinically meaningful activity when used in treatment-naïve patients with metastatic non–small cell lung cancer (NSCLC) who harbor EGFR exon 20 mutations, according to data from cohort 3 of the phase 2 ZENITH20 trial (NCT03318939) presented during the 2021 ESMO TAT Virtual Congress.¹

Of 79 patients, 12 remained on treatment with the agent, with a median follow-up of 9.2 months. Twenty-two patients achieved a response with poziotinib, equating to an overall response rate (ORR) of 27.8% (95% CI, 18.4%-39.1%). Moreover, the disease control rate (DCR) in these patients was 86.1%.

Additionally, preliminary data from cohort 5 of the trial showed that when the agent was delivered at a twice-daily dose in patients with metastatic NSCLC who harbored EGFR or HER2 exon 20 mutations, toxicity rates were reduced.

The treatment of this patient population represents a significant unmet need, according to lead study author Adrian Sacher, MD, of the Medical Oncology and Haematology Department at Princess Margaret Cancer Centre.²

In the open-label, multicenter phase 2 trial, investigators set out to evaluate the safety and efficacy of poziotinib in 7 patient cohorts of up to 603 previously treated and treatment-naïve patients with NSCLC.

To be eligible for enrollment to cohort 3, patients had to be treatment naïve with locally advanced NSCLC; they were allowed to have adjuvant/neoadjuvant therapies as long as they completed treatment at least 15 days before entering the study.³ Patients in cohort 5 had to have received at least 1 previous systemic treatment for locally advanced or metastatic NSCLC.

A total of 79 treatment-naïve patients with metastatic NSCLC and EGFR exon 20 mutations were enrolled to cohort 3, and they received poziotinib at a daily dose of 16 mg. Cohort 5 enrolled a total of 40 patients with NSCLC who harbored either EGFR or HER2 exon 20 mutations. These patients were randomized to different doses of poziotinib, including daily doses of either 10 mg, 12 mg, or 16 mg, as well as a twice-daily dose of 6 mg or 8 mg.

The primary end point of trial was ORR per RECIST v1.1 criteria, while secondary end points included DCR and DOR. Investigators also evaluated PFS in these patients.

Additional data from cohort 3 of the trial showed that the median DOR with poziotinib was 6.5 months. The majority, or 91%, of patients in the intent-to-treat population experienced tumor reduction with the treatment.

In this cohort, the safety profile of the agent proved to be comparable with second-generation EGFR TKIs, with 33% of patients experiencing rash that was grade 3 or higher in severity and 23% of patients reporting grade 3 or higher diarrhea.

Results from cohort 5 indicated that the toxicity rate in those who received a daily dose of poziotinib at 16 mg was 31% vs 21% with a twice-daily dose of 8 mg. Additionally, toxicity rates were 27% and 16% in those who received a daily dose of 12 mg vs a twice daily dose of 6 mg, respectively.

Moreover, data yielded from cycle 1 of treatment showed that twice daily dosing schedules of either 8 mg or 6 mg resulted in a relative reduction in dose interruptions by 38% and 52%, respectively.

References

1. Sacher A, Le X, Cornelissen R, et al. Safety, tolerability and preliminary efficacy of poziotinib with twice daily strategy in EGFR/HER2 exon 20 mutant non-smell cell lung cancer. Presented at: ESMO TAT Virtual Congress; March 1-2, 2021; Virtual. Accessed March 4, 2021

2. Poziotinib shows promise in EGFR and HER2 exon 20 mutated non-small cell lung cancer. News release. ESMO. March 2, 2021. Accessed March 4, 2021. http://bit.ly/3e7nqRF

3. Phase 2 study of poziotinib in patients with NSCLC having EGFR or HER2 exon 20 insertion mutation. ClinicalTrials.gov. Updated September 16, 2020. Accessed March 4, 2021. https://clinicaltrials.gov/ct2/show/NCT03318939