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The U.S. Food and Drug Administration has granted Breakthrough Therapy designation to the investigational third-generation epidermal growth factor receptor (EGFR) mutant-specific tyrosine kinase inhibitor (TKI), BI 1482694 (previously named HM61713).

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The designation is based on results from the Phase I/II HM-EMSI-101 clinical trial evaluating the treatment of T790M mutation-positive NSCLC in patients whose tumors have stopped responding to currently available EGFR-directed therapies.


BI 1482694, marketed by Boehringer Ingelheim, is a novel, third-generation, oral EGFR mutant-selective TKI developed to specifically target tumors with T790M mutations-considered the most common resistance mechanism to develop in response to treatment with EGFR TKIs and found in approximately 50 to 60 percent of patients who have previously received EGFR TKI therapy.


Results from HM-EMSI-101, a Phase I/II clinical trial of BI 1482694, provide additional evidence of the strong efficacy signals and favorable safety profile of BI 1482694 at the recommended Phase II dose of 800 mg once daily.


These data were presented at the ESMO Asia 2015 Congress in Singapore in December (Abstract 425PD) and at the ASCO Annual Meeting last spring (Abstract 8084).


In patients with T790M-positive NSCLC who had previously been treated with an EGFR TKI, objective responses by independent assessment were observed in 62 percent of patients, including 32 (46%) whose tumor response had been confirmed at the time of data cutoff. The disease control rate was 91 percent by independent assessment.


At the time of data cutoff, the median duration of response had not yet been reached and will be reported at a later date, according to a news release from the company.


The most common treatment-related adverse events were total/grade 3 diarrhea (55%/0%), nausea (37%/0%), rash (38%/5%), and skin itching (36%/1%).


The Global Phase II trial, ELUXA 1 (NCT02485652), is evaluating the efficacy and safety of BI 1482694 in patients with T790M mutation-positive NSCLC whose tumors stopped responding to currently available EGFR-directed therapies. The primary endpoint of this trial, which Boehringer Ingelheim describes as the first in a broad clinical development program for the agent, is objective response rate. There are currently several U.S. trial sites open.


Boehringer Ingelheim has an exclusive license and collaboration agreement with Hanmi Pharmaceutical Co. Ltd for the development and global commercialization rights of BI 1482694 (HM61713), except in South Korea, China, and Hong Kong.


The Phase I/II, multicenter HM-EMSI-101 study is assessing BI 1482694 in Korean patients. All patients included in the trial had been previously treated with at least one EGFR TKI and may have received additional lines of chemotherapy or other systemic treatments. At the recommended Phase II dose, all eligible patients had to have confirmed T790M mutation in the tumor. The primary endpoint was overall response, and secondary endpoints were duration of response, disease control rate, progression-free survival, and safety.