Bemcentinib Achieves Efficacy in Phase II NSCLC Trial, Setting Stage for Further Enrollment

Bemcentinib (BGB324) in combination with pembrolizumab (Keytruda) demonstrated clinical efficacy in the stage 1 portion of a phase II trial (BGBC008), which evaluated the combination in patients with non—small cell lung cancer (NSCLC) who progressed on prior immune checkpoint inhibition, meeting the primary end point of the study, according to a press release from BerGenBio ASA, developer of the drug.

Patients in stage 1 of the study who had received up to 2 prior lines of therapy, with the most recent line being a PD-1/PD-L1 inhibitor (Cohort B) met the efficacy end point with the confirmed response of at least 1 patient, meeting the criteria necessary for moving on to the second stage of the trial. In stage 2, 16 more patients with NSCLC who have previously progressed on an immune checkpoint inhibitor will be enrolled. Investigators will evaluate these patients to confirm the safety and clinical efficacy of bemcentinib plus pembrolizumab further.

“Reversing resistance to immune checkpoint inhibitors in patients who have relapsed on immunotherapy is a highly desirable alternative to the second-line chemotherapy standard-of-care,” Richard Godfrey, CEO of BerGenBio, said in a statement. “We are very excited with these early results in this challenging setting and look forward to expanding the study to confirm these findings and reporting comprehensive translational insight.”

The open-label, multicenter, single-arm study aims to assess the anti-tumor activity of this combination, as well as the safety of bemcentinib in combination with pembrolizumab. The trial consists of 2 cohorts; cohort A includes patients who have received up to 1 prior line of platinum-based chemotherapy and no prior immunotherapy.

To be included in this study, patients should meet the criteria for either Cohort A or Cohort B, have measurable disease defined by RECIST 1.1, have an ECOG performance score of 0 or 1, and have a life expectancy of at least 3 months. If patients are suitable for local therapy with curative intent, have received more than 1 prior line of chemotherapy, or have known additional malignancies, they are not eligible to enroll on this clinical trial to either cohort.

Patients will receive a loading dose of bemcentinib daily at 400 mg for 1 to 3 days, followed by 200 mg once daily. Pembrolizumab infusion was also given at 200 mg once every 3 weeks.

The primary outcome for the trial is objective response rate (ORR), which includes all patients who have a complete or partial response. Secondary end points include disease control rate, duration of response, time to progression, overall survival (OS), and adverse events (AEs). Investigators will also evaluate the correlation between response rate with baseline biomarkers in all patients.

According tofindings presented at the Society for Immunotherapy of Cancer’s 34^thAnnual Meeting(SITC 2019), the combination is well-tolerated in patients with AXL-positive NSCLC compared with were AXL-negative. The ORR in 44 patients that responded was 25%, and the disease control rate overall was 57%. The median progression-free survival in all 50 patients on the study was 4.1 months, but OS data were still maturing.

The most common all-grade AEs included transaminases in 38% of patients, asthenia/fatigue in 30%, and diarrhea in 24%. The occurrence of grade 3 AEs were minimal, whereas 7 patients had elevated transaminases (14%), 4 had asthenia/fatigue (8%), and 1 had anemia (2%). Discontinuation due to grade 4 pneumonia occurred in 1 patient, and grade 3 transaminases in 2 patients.

AXL kinase, a cell membrane receptor, is essential for mediating biological mechanisms of life-threatening diseases. AXL suppresses the body’s immune response to cancer tumors, leading to failure with many cancer treatments. Bemcentinib is a first-in-class selective AXL inhibitor, and this agent could potentially address a significant unmet medical need.

Trials are evaluating the AXL inhibitor in multiple solid and hematologic tumors, both as a single-agent and in combination with other therapies, such as immunotherapies, targeted therapies, and chemotherapies. The AXL inhibitor targets and binds to the intracellular catalytic kinase domain of the AXL receptor tyrosine kinase, leading to the inhibition of its activity.

AXL expression and immune modulation will be evaluated further in ongoing exploratory biomarker studies of both the tumor and blood samples. More data from this trial can be expected to be presented at an upcoming scientific meeting in 2020.

Reference:

BerGenBio Meets Efficacy Endpoint For First Stage Of Phase II Trial With AXL Inhibitor Bemcentinib in Combination With Keytruda in NSCLC Patients Progressing on Immune Checkpoint Inhibitors [news release]. Bergen, Norway: BerGenBio ASA; January 15, 2020. https://prn.to/38oqsLp. Accessed January 21, 2020.