Spectrum Pharmaceuticals Presents Results in HER2 Exon 20 Insertion Mutations from Cohort 2 of the Poziotinib ZENITH20 Clinical Trial

Spectrum Pharmaceuticals today presented additional results from its pivotal Phase 2 clinical trial, ZENITH20, evaluating poziotinib in previously treated non-small cell lung cancer (NSCLC) patients with HER2 exon 20 insertion mutations (Cohort 2). The on-demand mini oral session is part of the European Society for Medical Oncology (ESMO) Virtual Congress 2020 Science Weekend being held September 19 – 21, 2020.

“This is the first presentation to the medical and scientific community of the positive results from our registrational Cohort 2 from the ZENITH20 clinical trial,” said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. “There is no approved treatment for NSCLC patients with HER2 exon 20 insertion mutations, and we look forward to sharing this data with the FDA and discussing the path forward for poziotinib registration.”

The presentation titled “ZENITH20, a multinational, multi-cohort Phase 2 study of poziotinib in NSCLC patients with EGFR or HER2 Exon 20 mutations” is available to members of ESMO and can be accessed on the meeting website here: https://cslide.ctimeetingtech.com/esmo2020/attendee/confcal_1/session/list?q=poziotinib&r=st%7E12. A copy of the slides can also be found at: https://investor.sppirx.com/index.php/events-and-presentations.

ZENITH20 Trial Design and Results for Cohort 2

Cohort 2 of the ZENITH20 trial enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% CI, 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The disease control rate (DCR) was 70% while tumor reduction occurred in 67 patients (74%), with median tumor reduction of 22%. The evaluable patient analysis (n=74) demonstrated a confirmed ORR of 35.1% (95% CI, 24.4% – 47.1%) with a disease control rate of 82.4%.

The median duration of response was 5.1 months (range 1 to >12.3), with a median follow up of 8.3 months and the median progression free survival was 5.5 months (range 0 to >13.1). 13 patients (14%) had treatment-related serious adverse events and 11 patients (12%) permanently discontinued due to adverse events. Grade 3 treatment related rash was observed in 27 patients (30%) with diarrhea in 23 patients (26%). Stomatitis/mucosal inflammation Grades 3 and 4 occurred in 21 patients (23%). Dose interruptions were reported in 78 patients (87%), and dose reductions in 70 patients (78%), which was similar to the rates in Cohort 1.

Cohort 2 was designed to be a registrational study. Based on these results, Spectrum has requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss the data and its plans for a New Drug Application (NDA) submission.

The ZENITH20 trial is comprised of 7 independent cohorts. Cohorts 1 - 4 are each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR. Cohorts 5 - 7 are exploratory. In December 2019, the company reported that the primary endpoint for Cohort 1 (EGFR) was not met but clinical activity was seen. Based on the results of Cohort 1, the company has amended the protocol for ZENITH20 to explore additional twice-daily dosing regimens as well as lower single daily dosage. This amendment did not impact Cohorts 2 and 3 as these cohorts were fully enrolled. Top line results from Cohort 3 are expected by the end of the year.

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. The company holds an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by the company and Hanmi in several mid-stage trials in multiple solid tumor indications.

About Spectrum Pharmaceuticals, Inc. 

Spectrum Pharmaceuticals is a biopharmaceutical company focused on acquiring, developing, and commercializing novel and targeted oncology therapies. Spectrum has a strong track record of successfully executing across the biopharmaceutical business model, from in-licensing and acquiring differentiated drugs, clinically developing novel assets, successfully gaining regulatory approvals and commercializing in a competitive healthcare marketplace. Spectrum has a late-stage pipeline with novel assets that serve areas of unmet need. This pipeline has the potential to transform the company in the near future.

Related Posts

Subscribe Our Newsletter