Poziotinib, administered once daily at 16 mg, induced a median tumor reduction of 35% in patients with treatment-naïve non–small cell lung cancer (NSCLC) harboring HER2 exon 20 mutations, according to findings from cohort 4 of the ongoing phase 2 ZENITH20 trial (NCT03318939) that were presented at the 2021 ESMO Congress.1
“Most patients, 88%, show tumor reduction and a median tumor reduction of 35%,” said lead author Robin Cornelissen, MD, PhD, a pulmonologist with Erasmus MC Cancer Institute in Rotterdam, The Netherlands. “There are 3 patients with 100% decrease of the target lesions, however, 2 of those patients also had nontarget lesions and therefore were deemed as partial response.”
At a median follow-up of 13.5 months, the objective response rate (ORR) was 43.8% (95% CI, 29.5%-58.8%) with 1 (2.1%) complete response and 20 (41.7%) partial responses. Fifteen patients (31.3%) had stable disease and 7 (14.6%) had progressive disease; 5 patients (10.4%0 were not evaluable.
The disease control rate was 75%. The ORR, including unconfirmed response, was 47.9% (95% CI, 33.3%-62.8%). The median duration of response was 5.4 months (range, 2.8 to >19.1). The 6- and 1-year response duration rates were 42% and 24%, respectively.
The median progression-free survival (PFS) was 5.6 months (range, 0 to >20.2). The 6-month PFS rate was 42%; the 1-year PFS rate as 26%.
At present, there is no approved treatment for patients with HER2 exon 20 mutations, Cornelissen said. Studies exploring efficacy with current treatments—chemotherapy with our without immune checkpoint inhibitors and tyrosine kinase inhibitors (TKIs)—show ORRs from 6.9% to 35% and median PFS outcomes of 3 to 7 months. Furthermore, none of these current options are specific to exon 20 mutations.
In March, the FDA granted a fast track designation to poziotinib for use in previously treated patients with HER2 exon 20 mutations.2
ZENITH20 is a multicohort, multicenter, open-label trial examining the efficacy, safety, and tolerability of poziotinib, an oral, irreversible TKI targeting EGFR or HER2 exon 20 insertion mutations. In cohort 4 of the study, 48 patients with untreated locally advanced or metastatic NSCLC with HER2 exon 20 insertion mutations were assigned to 16 mg of poziotinib daily or 8 mg twice daily. Dose reductions were allowed if treatment-emergent adverse events (TEAEs) occurred. Patients were treated until intolerable toxicity, disease progression, or death.