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According to trial investigators, the results of the ongoing BFBC008 study point support the continued development of AXL inhibition with bemcentinib in order to extend the efficacy of immunotherapy in biomarker-selected refractory non–small cell lung cancer.
According to updated results from the phase 2 BGBC008 clinical trial (NCT03184571) presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC) Singapore, combination treatment with bemcentinib (BGB324) and pembrolizumab (Keytruda) in patients with checkpoint inhibitor (CPI)–naïve and CPI-refractory composite AXL (cAXL)–positive non–small cell lung cancer (NSCLC) was well tolerated and clinically active.
AXL is a mediator of resistance to immunotherapy and a negative prognostic factor for NSCLC. Given the results from this ongoing study, the investigators indicated a need to continue the development of AXL inhibition with bemcentinib in order to extend the efficacy of immunotherapy in biomarker-selected refractory NSCLC.
In an interview with CancerNetwork®, Jonathan Thompson, MD, MS, assistant professor in the division of Hematology/Oncology at the Medical College of Wisconsin, further explained the results of the study and what the investigators intend to focus on moving forward.
The main findings of [thes] current data [are that in] the checkpoint inhibitor–experienced patients, we did see at least 1 clinical response, objective response, in that group. That response was found in the cAXL-positive part of the cohort. cAXL positivity seems to enhance the sensitivity of the tumor to the combination of bemsentinib and pembrolizumab. The clinical benefit rate in the cAXL-positive group was also quite high at over 70%.
In contrast, the group that was cAXL negative tended to not have as high response rates. In fact, there [were] no objective responses [reported] in that group. There was a clinical benefit rate of about 20% in that group, so there does seem to be a signal that cAXL positivity is a potentially useful biomarker for this population. It should be noted that this is relatively early in cohort B. This was a report on 14 evaluable patients, and certainly we have ongoing recruitment to this study and we will be updating results as they come in.
Krebs MG, Helland Å, Carcereny Costa E, et al. A phase II study of the oral selective AXL inhibitor bemcentinib with pembrolizumab in patients with advanced NSCLC. Presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore; January 28-31, 2021; Virtual. Abstract OA01.07