New Agent for NSCLC Receives Breakthrough Therapy Designation

December 30, 2015
John Schieszer

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for BI 1482694, which is an investigational third-generation, epidermal growth factor receptor (EGFR), mutant-specific tyrosine kinase inhibitor (TKI) for patients with non-small cell lung cancer (NSCLC).

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for BI 1482694, which is an investigational third-generation, epidermal growth factor receptor (EGFR), mutant-specific tyrosine kinase inhibitor (TKI) for patients with non-small cell lung cancer (NSCLC).

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. 

The findings, which were presented at the European Society for Medical Oncology (ESMO) Asia 2015 Congress (abstract #426PD), demonstrated 62% objective responses in patients treated with this experimental agent, including 32 patients (46%) with confirmed tumor response.  

“Boehringer Ingelheim is pleased that the FDA has granted Breakthrough Therapy Designation to our investigational third-generation EGFR inhibitor BI 1482694. We feel this designation reflects the potential of the compound to be an important part of the treatment of non-small cell lung cancer in patients with T790M mutation,” said Tarek Sahmoud, MD, PhD, who is vice president of Oncology Clinical Development and Medical Affairs, in a press release.

BI 1482694 is a novel, third-generation, oral EGFR mutant-selective TKI that specifically targets tumors with T790M mutations. These T790M mutations are known as the most common resistance mechanism to develop in response to treatment with EGFR TKIs. They are found in approximately 50% to 60% of patients who have previously received EGFR TKI therapy, according to the investigators.

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.

In patients with T790M-positive NSCLC who had previously been treated with an EGFR TKI, objective responses (OR) were observed in 62% patients and in 46% patients whose tumor response had been confirmed at the time of data cut-off. Based on an independent assessment, the disease control rate was 91%.

At the time of data cut-off, median duration of response had not yet been reached and will be reported at a later date. The most common treatment-related adverse events (AEs) included diarrhea (55%), nausea (37%), rash (38%), and pruritis(36%).

The Global Phase II trial, ELUXA 1, has been initiated to evaluate 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 is objective response (OR) rate. This trial is the first in a broad clinical development program for BI 1482694.

The phase I/II, multicenter study of BI 1482694 was conducted in Korean patients who 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 (800 mg daily), all eligible patients had to have confirmed T790M mutation in the tumor. The primary endpoint was OR. The secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), and safety.