On September 5, 2018 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported new interim poziotinib data from the MD Anderson Phase 2 non-small cell lung cancer (NSCLC) study which appeared in an online abstract as part of the IASLC 19th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (Press release, Spectrum Pharmaceuticals, SEPT 5, 2018, View Source [SID1234529294]). The interim results, which include data from the EGFR cohort and, for the first time, the HER2 cohort, are preliminary and based on data through May 3, 2018. More robust and updated data will be presented in an oral session on September 24 at the conference in Toronto, Canada.
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"These results add to a growing body of evidence supporting the role of poziotinib in patients with EGFR and HER2 exon 20 mutations, and are a real advance for these patients for whom no targeted therapies have been effective so far," said John Heymach, M.D., Ph.D., Chairman and Professor, Department of Thoracic/Head and Neck Medical Oncology, University of Texas, MD Anderson Cancer Center. "I am highly encouraged by these results and the evolution of poziotinib data. Our study is the single largest data set in this high unmet need patient population and I am excited to present updated data during an oral session at the IASLC World Conference on Lung Cancer."
Data appearing in the abstract were current as of May 3, 2018. 40 patients of the 50 patient EGFR cohort had data available for the efficacy analysis. In the 40 patients, poziotinib continued to show robust efficacy with an objective response rate (ORR) of 58% in this heavily pre-treated population. Median progression free survival (PFS) was 5.6 months (95%-CI 5.06-NA). The disease control rate was 90%. In the HER2 cohort the ORR was 50% and the disease control rate was 83%. The most common adverse events were skin-rash (27.5%), diarrhea (12.5%), and paronychia (7.5%). 45.0% of patients required dose reduction to 12mg, while 17.5% of patients required dose reduction to 8mg. Updated data will be presented at the conference and will include data into September.
"We are thrilled with the data presented in the abstract and look forward to a more robust data set on September 24th," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "Additionally, we believe the treatment potential of poziotinib may go well beyond the previously treated lung cancer setting. We are actively expanding the poziotinib clinical program to explore poziotinib in new areas including first-line treatment of NSCLC, treatment of other solid tumors with EGFR or HER2 mutations, and combination therapies."
Spectrum Pharmaceuticals will be hosting a live webcast on September 24 following the oral presentation.
Abstract: A Phase II Trial of Poziotinib in EGFR and HER2 exon 20 Mutant Non-Small Cell Lung Cancer
Background
Insertions/mutations in exon 20 of EGFR and HER2 occur in ~1% and ~3% of all lung adenocarcinomas, respectively. These alterations are characterized by primary resistance to approved tyrosine kinase inhibitors (TKIs) with response rates of <12%. We have previously shown that exon 20 insertions restrict the size of the drug-binding pocket, limiting binding of large inhibitors. However, poziotinib can circumvent these steric changes and is a potent inhibitor of EGFR and HER2 exon 20 mutants (Robichaux et al. Nat Med). Herein, we report the results of an investigator-initiated study of poziotinib in EGFR and HER2 exon 20 mutant NSCLC (NCT03066206).
Methods
Patients ≥18yrs with locally advanced/metastatic NSCLC bearing mutations/insertions in EGFR or HER2 exon 20 (except EGFR T790M) were eligible. Unlimited prior systemic and targeted therapies were permitted. Poziotinib 16mg PO daily was administered until progression, death, or withdrawal. The primary endpoint was objective response rate (ORR) based on RECIST v1.1. Response was evaluated every eight weeks. A Bayesian design was used with a plan to enroll patients in cohorts of 10 and to terminate the study if ORR was ≤20%. Secondary endpoints included disease control rate (DCR); progression-free survival (PFS); overall survival; and safety.
Results
As of May 3, 2018, the planned EGFR cohort of 50 patients was fully enrolled, and 40 patients were evaluated for response. Median age was 55yrs (range 29-78). 65.1% of patients had received at least two prior lines of therapy for metastatic disease. 60% of patients had ≥grade 3 adverse events; most common were skin-rash (27.5%), diarrhea (12.5%), and paronychia (7.5%). 45.0% of patients required dose reduction to 12mg, while 17.5% of patients required dose reduction to 8mg. One patient stopped the treatment due to grade 3 skin rash. The ORR at eight weeks was 58% (95%-CI 40.9-73.0) and the DCR was 90% (95%-CI 76.3-97.2). Among 23 patients who achieved partial response, 15 responses were confirmed, five responses were unconfirmed, and three patients are pending confirmation. Responses were observed in 8/13 (62%) patients that were previously treated with TKI. Median PFS was 5.6mo (95%-CI 5.06-NA). Furthermore, 13 patients were enrolled in the HER2 cohort. Observed toxicities were similar to the EGFR cohort except one case of grade 5 pneumonitis, assessed to be possibly drug related. Twelve patients were evaluated for response with an ORR of 50% (95% CI 21.1-78.9) at eight weeks and a DCR of 83%.
Conclusion
The trial exceeded the stopping boundary of ORR of 20%. In a heavily pre-treated population with EGFR and HER2 exon 20 mutant NSCLC, poziotinib provides a high ORR, an encouraging PFS, and a manageable toxicity profile.
Conference Call Details:
Monday, September 24, 2018 @ 4:30 p.m. Eastern/1:30 p.m. Pacific
Domestic: (877) 837-3910, Conference ID# 1993267
International: (973) 796-5077, Conference ID# 1993267
The conference call will also be webcast live. To access the webcast and additional documents related to the call, please visit the Investor Relations page of the Spectrum Pharmaceuticals website at View Source
For interested individuals unable to join the call, a replay will be available from September 24, 2018 @ 7:00 p.m. ET/4:00 p.m. PT through October 1, 2018, until 7:30 p.m. ET/4:30 p.m. PT.
Domestic Replay Dial-In: (855) 859-2056, Conference ID# 1993267
International Replay Dial-In: (404) 537-3406, Conference ID# 1993267
About Poziotinib
Poziotinib is a novel, orally available 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. Spectrum received an exclusive license from Hanmi Pharmaceuticals to develop, manufacture, and commercialize worldwide excluding Korea and China. Poziotinib is currently being investigated by Spectrum and Hanmi in several mid-stage trials in multiple solid tumor indications.
The poziotinib NSCLC clinical program for patients with EGFR or HER2 exon 20 insertion mutations currently consists of a Phase 2 investigator-initiated study at The University of Texas MD Anderson Cancer Center and a Phase 2 pivotal, Spectrum-sponsored, multi-center, global study (ZENITH20) with active sites in the United States and future centers planned in Canada and Europe.