Luye Pharma (HKEx: 02186) has signed a license agreement with Hanmi Pharmaceutical (KRX:128940) to co-develop poziotinib (HM781-36B, NOV120101). Hanmi will receive upfront and milestone payments up to $20 million.
Poziotinib is an irreversible pan-HER inhibitor, inhibiting EGFR, HER2, HER4 with IC50 values of 3.2 nM, 3.5 nM, and 23.5 nM, respectively.
To my knowledge, quinazoline-based EGFR inhibitors don’t work in NSCLC patients harboring T790M mutation.
The second-generation, irreversible EGFR inhibitors such as afatinib, neratinib, dacomitinib demonstrated significant preclinical activity in T790M-mutant lung cancer cell lines and mice models. However, these agents had limited success in clinical trials.
Luckily, the third-generation nonquinazoline-based EGFR inhibitors such as rociletinib (CO-1686) and AZD9291 are promising in patients with T790M mutation.
Poziotinib is an anilino-quinazoline-based EGFR inhibitor. Although inhibiting EGFR T790M mutant in vitro, poziotinib may repeat the failure of afatinib in erlotinib/gefitinib-resistant NSCLC.
Table 1. Summary of afatinib and poziotinib in rlotinib/gefitinib-resistant NSCLC
|afatinib||697||3.3 months||10.8 months||7%||diarrhoea (17%), rash (14%)|||
|poziotinib||27||11.4 weeks||NA||12%||diarrhoea (18.5%), decreased appetite (7.4%)|||
In addition to erlotinib/gefitinib-resistant NSCLC (phase II), poziotinib is currently being investigated in lung adenocarcinoma (first line, phase II), HNSCC (phase II), HER2 positive gastric cancer (phase II), and HER2 positive breast cancer (phase II).
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 Lancet Oncol. 2012, 13(5), 528-538.
 Results from phase I studies (NCT01455571, NCT01455584). WCLC2013, Abstract # 2029.