Poziotinib Update after Successful Pre-NDA Meeting with FDA while Cohort 3 did not meet its primary endpoint.
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 4:30 p.m. ET / 1:30 p.m. PT
December 22, 2020 04:05 PM Eastern Standard Time HENDERSON, Nev.--(BUSINESS WIRE)--Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, today announced that the U.S. Food and Drug Administration (FDA) has agreed to the submission of an NDA based on data from Cohort 2 of its Phase 2 clinical trial, ZENITH20, which evaluated previously treated patients with non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations. The company also reported that its pre-specified primary endpoint in its Phase 2 clinical trial evaluating poziotinib in first-line NSCLC patients with EGFR exon 20 insertion mutations was not met in Cohort 3. Spectrum additionally reported that preliminary data from patients receiving 8 mg of poziotinib twice daily demonstrated meaningful improvement in tolerability as measured by adverse events and dosing interruptions.
“While Cohort 3 did not meet its pre-specified ORR endpoint, we are seeing evidence of clinical activity with a disease control rate (DCR) of 86% and progression free survival data of 7.2 months.”
Tweet this “The agreement with the FDA to proceed with the submission of a new drug application is a significant milestone for the poziotinib program,” said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. “The improved tolerability from the BID dosing could have a meaningful impact on the overall safety and efficacy profile of poziotinib in an area of high unmet medical need.”
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 Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. “While Cohort 3 did not meet its pre-specified ORR endpoint, we are seeing evidence of clinical activity with a disease control rate (DCR) of 86% and progression free survival data of 7.2 months.” Dr. Lebel added, “The preliminary data from Cohort 5 with 8 mg twice daily dosing is supporting our hypothesis that this new dosing paradigm improves tolerability substantially, with Grade 3 adverse events reduced by about a third. We believe that improved tolerability and reduced drug dosing interruptions are key to patients staying on the drug longer and could potentially enhance anti-tumor effectiveness across the various EGFR and HER2 cohorts. These early findings, if confirmed, could benefit the entire poziotinib program.”
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, December 22, 2020, at 4:30 p.m. ET / 1:30 p.m. PT. The live call may be accessed by dialing (877) 837-3910 for domestic callers and (973) 796-5077 for international callers and entering the conference ID#: 5036836. A live webcast of the call will be available from the Investor Relations section of the company’s website at https://investor.sppirx.com/events-and-presentations and will be archived there shortly after the live event.
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.
My thinking is if any news will be negative it will be regarding cohort 3 w the once a day 16 mg dosing.
It seems Cohort 3 just missed
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%.
I would think they'll redo cohort 3 w the less toxic bid dosing since were able to tolerat it more but will listen to the CC at 4:30 to confirm that's the case.
