FDA Grants Fast Track Designation to Bemcentinib/PD-L1 Therapy for AXL+ Advanced/Metastatic NSCLC


The FDA has granted fast track designation to bemcentinib in combination with an anti-PD-L1 agent as a potential treatment option for patients with AXL-positive advanced or metastatic non-small cell lung cancer.

The FDA has granted fast track (FTD) designation to bemcentinib (formerly known as BGB324) in combination with an anti-PD-L1 agent as a potential treatment option for patients with AXL-positive advanced or metastatic non-small cell lung cancer (NSCLC), according to a press release by BerGenBio ASA.1

The designation has been granted for patients without actionable mutations, who experienced disease progression on or after treatment with an anti-PD-L1 agent, with or without chemotherapy as their frontline treatment method. The decision marks the first time in history that AXL-positive disease is recognized as a molecular targetable disease by the FDA.

"Building on our encouraging clinical and translational data, we are excited to receive fast track designation from the FDA for the promising combination of bemcentinib in combination with a checkpoint inhibitor. This regulatory milestone is particularly meaningful for BerGenBio, as it represents the first formal recognition by a regulator of AXL-positive patients as a discernible patient population and serves as further validation of our belief that AXL inhibition has high potential as a cornerstone of cancer combination therapy, said Richard Godfrey, chief executive officer, BerGenBio, in a statement. We look forward to working closely with the FDA on the continued clinical development of the combination."

During the 2021 World Conference on Lung Cancer held in January, findings from bemcentinib in combination with the anti-PD-L1 therapy, pembrolizumab (Keytruda) were reported and showed that the combination induced responses in patients with checkpoint inhibitor (CPI)-naïve and CPI-refractory composite AXL-positive NSCLC treated in the phase 2 BGBC008 clinical trial (NCT03185471). The bemcentinib doublet was also well-tolerated in patients.2

Patients included in the single-arm, 2-stage study received bemcentinib 200 mg per day and pembrolizumab 200 mg, every 3 weeks.The primary end point of the study was objective response rate (ORR) per RECIST 1.1 with pre-defined criteria. The secondary end points were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

The AXL-positive population achieved an ORR of 33% on treatment with bemcentinib plus pembrolizumab with a clinical benefit rate (CBR) of 73%. In comparison, those with AXL-negative advanced or metastatic NSCLC had an ORR of only 7% and a CBR of 40%.

In the subset of patients in the study who were on prior CPI therapy, the ORR achieved with bemcentinib plus pembrolizumab was14% with a CBR of 84%, in the AXL-positive group. In the AXL-negative group, objective responses were not observed for a CBR of only 29%.

The safety profile of bemcentinib/pembrolizumab consistent with that of either drug alone. In comparison with docetaxel, the toxicity profile of the combination was considered favorable.

Treatment-related adverse events (TRAEs) were observed ≥10% of patients who received the combination. The TRAEs included increased alanine aminotransferase (ALT; 33%), increased aspartate aminotransferase (AST; 32%), diarrhea (32%), asthenia (19%), pruritus (16%), nausea (15%), increased blood creatinine (13%), prolonged electrocardiogram QT (13%), fatigue (13%), anemia (12%), and decreased appetite (11%). One hundred percent of the treatment-related ALT and AST increase occurrences were reversible and managed with steroids and treatment interruption.

With an FTD, the developer of bemcentinib will have more frequent meetings with the FDA to discuss further development of the agent. An FTD also makes bemcentinib eligible to be granted accelerated approval by the FDA later on.


1. BerGenBio receives FDA fast track designation for bemcentinib / anti-pd-(l)1 combination in NSCLC. News release. BerGenBio ASA. June 8, 2021. Accessed June 9, 2021.

2. 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

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