NEW YORK – Spectrum Pharmaceuticals said Thursday that its drug candidate poziotinib failed to meet the pre-specified primary endpoint in the first cohort of participants in a Phase II clinical trial investigating patients with pretreated non-small cell lung cancer (NSCLC) harboring EGFR exon 20 mutations.
The company said it will continue to study the drug in other molecularly defined patient cohorts and provide a full read out of the outcomes in this subset of patients in 2020.
Poziotinib is an experimental EGFR inhibitor. The Phase II ZENITH20 trial’s cohort 1 consisted of 115 patients. Out of these, 17 patients had a response to the drug and 62 patients had stable disease with a 68.7 percent disease control rate. The objective response rate was 14.8 percent, and the median duration of response was 7.4 months. The drug was relatively safe compared to other second-generation EGFR tyrosine kinase inhibitors on the market.
“While the response rate of cohort 1 in this trial was lower than we expected, the positive signals observed for this cohort provide support for the continued clinical evaluation of poziotinib in this patient population with significant unmet medical need," said Spectrum CEO Joe Turgeon. "We look forward to providing read outs from cohorts 2 and 3 in 2020, and plan to provide an update on the overall program strategy during the first quarter of 2020 after a full evaluation of the data from cohort 1 is completed.”
The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR exon 20 mutation) and 2 (HER2 exon 20 insertion mutations) contain previously treated NSCLC patients with exon 20 mutations. Cohort 3 (EGFR exon 20 insertion mutations,) and 4 (HER2 exon 20 insertion mutations) are investigating NSCLC patients with exon 20 mutations in the first-line setting. Cohorts 1- 4 are independent trials testing a prespecified statistical hypothesis. The primary endpoint is objective response rate.
In July 2019, the company added three new exploratory cohorts to the ZENITH20 study. Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with EGFR mutations who progressed from first-line osimertinib treatment but developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21. Studies for cohorts 4-7 are still in progress.