Bemcentinib for NSCLC Granted FDA Fast Track Designation

The FDA has granted an FDA fast track designation to bemcentinib (BGB324) in combination with an anti-PD-(L)1 agent for the treatment of STK11-mutated advanced/metastatic non-small cell lung cancer (NSCLC), according to a press release by BerGenBio ASA.¹

Bemcentinib is an anti-AXL inhibitor. A mouse model found that in mice sensitive to PD-1 blockade, systemic AXl inhibition using bemcentinib caused the expansion of tumor-associated T cells along with restoring therapeutic response to anti-PD-1 check point inhibitors.

Currently, bemcentinib is being studied in combination with pembrolizumab (Keytruda) in a phase 2 trial (NCT03184571). The single-group assignment trial has an estimated enrollment of 106 participants and an estimated completion date of September 2022. The primary end point in objective response rate. Secondary end points include disease control rate, duration of response, progression-free survival, overall survival, adverse events (AEs), and pharmacokinetics.²

The trial is split into 3 cohorts. In all cohorts, patients will receive bemcentinib 400 mg capsules for days 1 through 3 and 200 mg thereafter. Pembrolizumab will be administered every 3 weeks as a 200 mg infusion. Cohort A will include patients who received a maximum of 1 prior line of platinum-containing chemotherapy an no prior immunotherapy of any kind. Cohort B will be made up of patients who received a maximum of 1 prior line of an anti-PD-L1 monotherapy. Cohort C will enroll patients who received a maximum of 1 prior line of therapy with an anti-PD-L1 therapy in combination with platinum-containing chemotherapy.

Data found that of the 3 evaluable patients with identified STK11/LKB1 mutations, all 3 demonstrated objective clinical response and/or benefit to treatment with the bemcentinib/pembrolizumab combination. In a 2018 interim analysis, 11 of 13 patients included in the analysis remained on study treatment. Additionally, the combination was found to be well tolerated, with the overall serious AE profile being similar to pembrolizumab monotherapy. Of the 4 patients who reached their first scan, 1 achieved a partial response and another had stable disease. No treatment-related AEs that were grade 4 in nature were reported. Dose reduction was required in 12% of patients.³ 

In order to participate in the study, patients must have confirmed stage IV adenocarcinoma NSCLC, measurable disease, an ECOG score of 0 or 1, a life expectancy of at least 3 months, and adequate organ function. Patients with disease suitable for local therapy have received more than 1 prior line of therapy, a known additional malignancy, active central nervous system metastases, an active autoimmune disease, known lactose intolerance, or major surgery within 28 days prior to the start of the study are not eligible to participate.

The study is currently recruiting in New Hampshire and Wisconsin.

_REFERENCES:

_{1.BerGenBio receives FDA fast track designation for bemcentinib in STK11-mutated advanced/metastatic non-small lung cancer (NSCLC). News release. BerGenBio. November 9, 2021. Accessed November 10, 2021. https://bit.ly/3og7UXb}

_{2.Bemcentinib (BGB324) in combination with pembrolizumab in patients with advanced NSCLC. ClinicalTrials.gov. Accessed November 10, 2021. https://bit.ly/3H9eGGT.}

_{3.Lorens J, Arce-Lara C, Arriola E, et al. Phase II open-label, multi-centre study of bemcentinib (BGB324), a first-in-class selective AXL inhibitor, in combination with pembrolizumab in patients with advanced NSCLC. J Clin Oncol. 2018;26(15):3078. doi: 10.1200/JCO.2018.36.15_suppl.3078}