Fast track application is based on positive data in HER2 exon 20 insertion mutations in previously treated patients.
Spectrum Pharmaceuticals, a biopharmaceutical company with a focus on novel and targeted oncology therapies, has submitted a new drug application (NDA) to the FDA for poziotinib for individuals with previously treated locally advanced or metastatic non–small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations, the company said in a statement.
The NDA is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the efficacy and safety of poziotinib, which previously received Fast Track designation from the FDA. There is no treatment specifically approved for this indication.
“The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer,” Joe Turgeon, president and CEO of Spectrum Pharmaceuticals, said in the statement. “I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need.”.
Cohort 2 had 90 individuals enrolled who received an once-daily, oral dose of 16mg of poziotinib. Investigators found that the intent-to-treat analysis demonstrated a confirmed objective response rate of 27.8%, and 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.
About 87% of individuals of this cohort had drug interruptions with 11 individuals, or 12%, permanently discontinuing because of adverse events (AEs).
About 14% of individuals had treatment-related AEs.
The findings for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology.
The ZENITH20 study consists of 7 cohorts of individuals with NSCLC. Cohorts 1, focused on EGFR, and 2, focused on HER2, enrolled individuals with NSCLC who were previously treated with exon 20 mutations. Cohort 3, focused on EGFR, enrolled first-line individuals with NSCLC. Cohort 4 (HER2) is enrolling first-line individuals with NSCLC with exon 20 mutations.
Cohorts 1 through 4 are independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate.
Cohort 5 includes individuals with NSCLC with EGFR or HER2 exon 20 insertion mutations who were previously treated or treatment naïve. Cohort 6 includes individuals with NSCLC with classical EGFR mutations who progressed while on treatment with first-line Osimertinib and developed an additional EGFR mutation. Cohort 7 includes individuals with NSCLC with a variety of less common mutations in EGFR or HER2 exons 18 through 21 or the extracellular or transmembrane domains.
The company had a successful pre-NDA meeting with the FDA, resulting in an agreement to submit an NDA for poziotinib.
During this meeting, Spectrum confirmed with the FDA that the Cohort data could be a basis of an NDA submission.
Spectrum will continue to work with the FDA as appropriate while the review is conducted.
Spectrum Pharmaceuticals submits new drug application for poziotinib. Businesswire. News release. December 6, 2021. Accessed December 8, 2021. https://www.businesswire.com/news/home/20211206005311/en/Spectrum-Pharmaceuticals-Submits-New-Drug-Application-for-Poziotinib