"This interim clinical and translational data add further confidence to the potential patient benefit of selective AXL inhibition with bemcentinib, to reverse resistance to immune checkpoint inhibitors in selected cAXL-positive patients who have relapsed on immunotherapy."
The majority of checkpoint inhibitor refractory, composite AXL (cAXL)-positive patients with non–small cell lung cancer (NSCLC) experienced clinical benefit with the combination of bemcentinib (BGB324) with pembrolizumab (Keytruda), according to interim findings from the phase 2 BGBC008 clinical trial (NCT03184571) announced by BerGenBio.
In January 2020, the company announced that stage 1 of this trial met its primary end point of overall response rate, and the criteria were met for expansion of this cohort to stage 2.
"This interim clinical and translational data add further confidence to the potential patient benefit of selective AXL inhibition with bemcentinib, to reverse resistance to immune checkpoint inhibitors in selected cAXL-positive patients who have relapsed on immunotherapy,” stated Richard Godfrey, chief executive officer, BerGenBio.
In cohort B of stage 1, which included 12 evaluable patients for cAXL, 7 patients were cAXL-positive, and 6 reported clinical benefit with the combination regimen; 1 patient had a partial response and 1 had an unconfirmed partial response. There was a 2.5-fold improvement in the median progression-free survival in this cohort as well.
A third cohort, cohort C, will included patients in the second-line setting who are refractory to first-line checkpoint inhibition combined with chemotherapy. Cohorts B2 and C continue to enroll and are actively recruiting patients. Topline data are expected to be presented toward the end of the year 2020.
“This [strategy] would be a highly desirable alternative to the second-line chemotherapy standard-of-care. Top line data from expansion cohorts B2 and cohort C should be available towards the end of 2020," Godfrey added.
In the cAXL-positive patients in cohort A, the 12-month overall survival (OS) rate was 79%, and the median OS was 17.3 months, although data are still maturing. In patients who were cAXL-negative, the 12-month OS rate was 60%, and the median OS was 12.4 months, which is in-line with historical controls.
Bemcentinib is a potent first-in-class selective AXL inhibitor under evaluation in a broad phase 2 clinical development program. Trials are ongoing for this agent as treatment of multiple solid and hematologic tumors, both alone and in combination with current and emerging therapies, such as immunotherapies, targeted therapies, and chemotherapy.
AXL is known to suppress immune response to tumors and ultimately drives cancer treatment failure in many indications. Expression of AXL is associated with very poor prognosis in most cancer types. Therefore, the AXL inhibitors may play an important role in combination regimens, addressing a significant unmet need.
The AXL inhibitor bemcentinib binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase to inhibit its activity. Increased AXL function has been associated with key mechanisms of drug resistance and immune escape, which leads to more aggressive metastatic disease in patients with cancer.
In this open-label, multicenter, single-arm study, investigators aim to assess the anti-tumor activity and safety of the combination regimen in up to 77 patients with previously treated advanced adenocarcinoma of the lung. The study includes 2 cohorts of patients; in cohort A, patients must have received a maximum of 1 line of platinum-based chemotherapy and have no prior immunotherapy, and cohort B includes patients with a maximum of 2 prior lines of therapy, whereas the most recent line must have included a PD-L1 inhibitor.
Secondary end points in this study include disease control rate, duration of response, time to progression, OS, and number of patients with adverse events.
To be eligible for the study, patients must have measurable disease by RECIST 1.1, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function at the time of screening within 10 days of treatment initiation. Patients cannot participate in the clinical trial if they have disease suitable for a local therapy of curative intent, had a known additional malignancy that is progressing or requires active treatment, or had known active central nervous system metastases or carcinomatous meningitis.
BerGenBio announces positive interim clinical and translational data from phase ii trial of bemcentinib in combination with Keytruda in checkpoint inhibitor refractory NSCLC patients. News Release. BerGenBio. June 25, 2020. Accessed June 25, 2020. https://prn.to/31dSlp7