Spectrum Provides Poziotinib Update after Successful Pre-NDA Meeting with the FDA
FDA agrees to the submission of an NDA for poziotinib for non-small cell lung cancer (NSCLC) in previously treated patients with HER2 exon 20 insertion mutations, NDA submission planned for 2021
Cohort 3 of the ZENITH20 clinical trial, which enrolled first-line NSCLC patients with EGFR exon 20 insertion mutations at 16mg once daily, did not meet its primary endpoint
Preliminary data from 8 mg twice daily dosing demonstrates meaningful improvement in tolerability
Management to host webcast and conference call today at
“The agreement with the FDA to proceed with the submission of a new drug application is a significant milestone for the poziotinib program,” said
The company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as it prepares the application for submission in 2021. Cohort 2 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% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events.
“We are pleased that the FDA meeting confirmed that Cohort 2 data can serve as the basis of a NDA submission and our team is diligently working on preparing our file for submission in 2021,” said
Cohort 3 of the ZENITH20 clinical trial enrolled a total of 79 patients who received an oral once daily dose of 16 mg of poziotinib. The median time of follow up of all patients was 9.2 months with 12 ongoing patients still on treatment. The intent-to-treat analysis showed that 22 patients had a partial response (by RECIST) and 68 patients had stable disease for an 86.1% DCR. 91% of patients experienced tumor reduction with a median reduction of 25.5%. The confirmed ORR was 27.8% (95% CI 18.4-39.1%). Based on the pre-specified statistical hypothesis for the primary endpoint, the observed lower bound of 18.4% did not meet the pre-specified lower bound of >20%. The median duration of response was 6.5 months and the median progression free survival was 7.2 months. The safety profile was similar with the type of adverse events observed with other second-generation EGFR tyrosine kinase inhibitors. Grade 3 treatment related rash was 33% and diarrhea was 23%. 94% of patients had drug interruptions with 6 patients (8%) permanently discontinuing due to adverse events.
Preliminary data from Cohort 5 for patients with exon 20 insertion mutations receiving 8 mg twice daily dosing shows improved tolerability versus patients who received the 16 mg once daily dose. The data from this cohort includes patients with both EGFR and HER2 mutations. In Cycle 1, the incidence of Grade 3 or higher treatment related adverse events (rash, diarrhea and stomatitis) decreased by 32% for patients receiving the 8 mg twice daily dose. In addition, dose interruptions were reduced by 38% for the 8 mg twice daily dose versus the 16 mg once daily dose. No new types of adverse events were observed with the twice daily dosing regimen.
Conference Call and Webcast
The company’s management will host a webcast and conference call today,
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
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
Notice Regarding Forward-Looking Statements
Certain statements in this press release may constitute “forward-looking statements” within the meaning of the United States Private Securities Litigation Reform Act of 1995, as amended to date. These forward-looking statements relate to a variety of matters, including, without limitation, statements that relate to the company’s business and its future, including the significance of Cohort 3’s reported results; the significance of the preliminary data from Cohort 5, including, but not limited to, whether the new dosing paradigm will continue to improve tolerability, lead to patients staying on the drug longer and enhance anti-tumor effectiveness and the impact of such data on the entire poziotinib program; the timing and outcome of filing an NDA with Cohort 2 data with the FDA; the overall determination of a path forward for poziotinib; poziotinib’s potential to significantly advance the treatment of NSCLC patients with EGFR or HER2 exon 20 insertion mutations; the timing and result of future FDA approvals; the overall progression of the poziotinib development program; the company’s ability to advance development of its late-stage pipeline assets and such assets’ ability to serve areas of unmet need; the potential of the company’s existing drug pipeline to transform the company in the near future; and other statements that are not purely statements of historical fact. These forward-looking statements are made on the basis of the current beliefs, expectations, and assumptions of the management of the company and are subject to significant risks and uncertainties that could cause actual results to differ materially from what may be expressed or implied in these forward-looking statements. Risks that could cause actual results to differ include the possibility that the different methodologies, assumptions and applications the company utilizes to assess particular safety or efficacy parameters may yield different statistical results, and even if the company believes the data collected from the clinical trials of its product candidates, including poziotinib, are positive, these data may not be sufficient to support approval by the FDA; the possibility that success in early clinical trials, especially if based on a small patient sample, might not result in success in later clinical trials, and other unforeseen events during clinical trials which could cause delays or other adverse consequences; the company’s existing and new drug candidates, including poziotinib, may not prove safe or effective; the possibility that the company’s existing and new applications to the FDA and other regulatory agencies, including the NDA with Cohort 2 data it plans to submit in 2021, may not receive approval in a timely manner or at all; the possibility that the company’s existing and new drug candidates, including poziotinib, if approved, may not be more effective, safer or more cost efficient than competing drugs; the possibility that the company’s efforts to acquire or in-license and develop additional drug candidates may fail; the company’s dependence on third parties for clinical trials, manufacturing, distribution and quality control and other risks that are described in further detail in the company's reports filed with the
Managing Director, Westwicke ICR
Chief Financial Officer