The Disease Control Rate is as High as 90%! Korean and American Refractory Lung Cancer Drug Poziotinib is Coming!

EGFR is a common mutation in non-small cell lung cancer (NSCLC), about 10% of patients with lung cancer with EGFR exon 20 mutation, the current generation of TKI (gefitinib, erlotinib, ectinib), second generation TKI (Afatinib) and three generations of TKI (Ochitinib) are ineffective and belong to refractory lung cancer. The emergence of Poziotinib will make up for this deficiency. Expect Poziotinib to benefit more patients. 

Currently available EGFR-TKI is active against most EGFR mutations in NSCLC, but different targeted drugs have different effects on different mutations, with the least inhibitory effect on Ins20.

About 50% of non-small cell lung cancers in the Asian population have activated EGFR mutations. Among the EGFR mutations, the most common appear in the 18-21 exon, of which more than 80% of the mutations in the 19 exons (Del19) and 21 exons (L858R), are the main population of oral EGFR targeted drug therapy. . 

The rest are rare mutations, including G719X, E709X, Del18 on the 18 exons, 19Ins on the 19 exons, S768I on the 20 exons, and L861Q on the 21 exons, but they can Benefited from the drug afatinib.
The 20-exon insertion mutation 20Ins and the point mutation T790M are resistant mutations to EGFR-targeted drugs. Among them, Oxitinib has been approved for T790M, and there is no drug listed for 20ins. Currently, its ORR is only 3-8%, and PFS is 2 months.

In addition, approximately 3% of NSCLC patients carry HER2 mutations, of which approximately 90% are 20 exon mutants of the HER2 gene. Overall, EGFR/HER2 exon 20 mutant patients accounted for approximately 4% of all NSCLC patients; however, due to the high number of lung cancer cases in China, this group of patients should not be ignored. For these patients, the current efficacy of targeting TKIs is limited, so new treatments are urgently needed. 

Developed by Hanmi, Poziotinib is currently the world's highest development stage for clinical phase II. It is a novel oral quinazoline broad-spectrum HER inhibitor that irreversibly blocks HER family tyrosine kinase receptors (including HER1, HER2 and HER4). The signaling pathway, thereby inhibiting the proliferation of tumor cells that overexpress these receptors. Spectrum has obtained exclusive licenses from Korea and the United States in addition to South Korea and China, while Luye Pharmaceutical has obtained exclusive development, production and commercialization licenses for Poziotinib China. 

In vitro studies and PDX model studies and genetically engineered mouse models have shown that Poziotinib has a better inhibitory effect on EGFR/HER2 exon 20 mutant NSCLC than FDA-approved EGFR-TKIs.

Based on the inspiring results of preclinical studies, the MD Anderson Cancer Center conducted a multicenter phase II trial in which Poziotinib treats lung cancer exon 20Ins with a disease control rate of up to 90% (complete response partial response stable disease), HER2 The patient's disease control rate was 83%. The results of this study were reported at the WCLC meeting in 2018. The best ORR for EGFR 20Ins mutations was 55%, the confirmed ORR was 43%, and the median PFS was 5.5 months. Historical data show that the patient's ORR for the current first-line EGFR-TKI treatment is only 3-8%, and the PFS is only 2 months.

For the efficacy of the HER2 exon 20ins mutant NSCLC, the patient's best ORR was 50%, the confirmed ORR was 42%, and the median PFS was 5.1 months. The efficacy was similar to that of the EGFR exon 20 mutation.

According to the New Drug Development Monitoring Database (CPM), Poziotinib has developed or plans to include indications for breast cancer, solid tumors, and stomach cancer, except for small cell lung cancer.

For patients with EGFR/HER2 exon-mutant lung cancer, the current generation of TKI (gefitinib, erlotinib, ectinib), second-generation TKI (afatinib), three-generation TKI (Oxi) It is ineffective and belongs to refractory lung cancer. The emergence of Poziotinib will make up for this deficiency. Expect Poziotinib to benefit more patients.

The original news release could be found here in Chinese: