Bemcentinib Granted FDA Fast Track Designation for R/R AML

Bemcentinib, a first-in-class AXL inhibitor, has been approved for a fast track designation by the FDA for the treatment of elderly patients with relapsed or refractory acute myeloid leukemia, according to a press release from BerGenBio.<br /> &nbsp;


"We are thrilled that bemcentinib has been granted Fast Track Designation.Not only does this make us eligible for accelerated approval and priority review, but it serves as an important validation of bemcentinib in this significant unmet medical need we are trying to address. Currently, bemcentinib is in expanded phase II trials in the United States and Europe for the treatment of AML and the Company has recently announced positive interim top-line data,” said Richard Godfrey, chief executive officer, BerGenBio ASA, in the press release.

This designation comes on the heels of promising phase Ib and preliminary phase II data presented at the 2019 EHA Annual Congress.2,3

In the phase Ib/II study of bemcentinib plus cytarabine or decitabine in patients with AML who are unfit for intensive chemotherapy (NCT02488408), investigators looked for signs of anti-leukemic activity and evaluated the safety and efficacy of the combination. Another important experimental arm in this trial looked at bemcentinib as a single agent in patients with AML.

The study was open to patients who were newly diagnosed with AML or previously treated with cytotoxic chemotherapy, as well as pretreated patients with MDS aged 18 years and older. Patients with unstable cardiac disease, congestive cardiac failure, an abnormal left ventricular ejection fraction, unresolved CTCAE toxicity above grade 2 and active, or uncontrolled central nervous system (CNS) disease, including CNS leukemia, were excluded from the study.

A total of 16 patients with AML were enrolled in the combination part of the phase II study and received bemcentinib (200 mg daily) plus low-dose cytarabine in 21-day cycles. Among these patients, 14 were evaluable for response in the preliminary analysis and 6 patients did respond to treatment.

Complete responses (CRs) were seen in 4 patients and 2 had partial responses. Five of these patients were older than 75 years. The relapse-free survival rate in patients who achieved a CR or CR with incomplete hematologic recovery (CRi) was 7.9 months (range, 0.7-9.6). An additional 2 patients achieved stable disease lasting at least 3 months.4

The treatment was considered tolerable despite the occurrence of treatment-related adverse events (TRAEs) seen in 15% of patients. The most common TRAEs were anemia, neutropenia, and diarrhea.

In the phase Ib dose-escalation portion of the study, bemcentinib was also evaluated as a single agent in patients with AML and MDS to see how the drug affects the AXL signaling pathway.3Twenty-five patients were enrolled, and of those patients, 21 had relapsed/refractory AML. The other 4 patients had MDS. These patients received varying loading and continuation doses of bemcentinib in a classical 3+3 dose-escalation design: 400/100 mg, 600/200 mg, and 900/300 mg. Then, to see how the monotherapy was affecting the AXL signaling pathway, investigators took frequent peripheral blood and bone marrow samples; the samples were analyzed using the TruSight myeloid panel (Illumina).

The results showed that signaling in circulating leukemic blasts was altered in 11 patients. These alterations were observed in proteins pPLCγ1, pErk, and pAkt; however, they did not affect the clinical response the investigators reported. The blood samples did provide important information about the blast populations in 7 of the patients, leading investigators to the conclusion that peripheral blood is best for observing the unique pharmacodynamic properties and signaling responses that were found in this study.

The phase Ib/II study is key for the further development of bemcentinib, which the developer believes can serve an unmet need for patients with AML. BerGenBio is planning to hold frequent meetings and have more communication with the FDA overall to discuss the drug’s continued development, the design of clinical trials, the use of biomarkers, and the process for potentially getting the drug approved for the treatment of elderly patients with relapsed/refractory AML.


  1. BerGenBio Receives FDA Approval of Fast Track Designation for Bemcentinib [press release]. Bergen, Norway: BerGenBio; October 22, 2019. Accessed October 22, 2019.
  2. Loges S, Heuser M, Chromik J, et al. The combination of bemcentinib, a novel, oral, selective axl-inhibitor and low-dose cytarabine yields durable responses in aml patients unfit for intensive chemotherapy. Presented at: 2019 EHA Congress; June 13-16, 2019; Amsterdam, Netherlands. Abstract PF259.
  3. Helles&oslash;y M, Fagerholt OH, Tislevoll, BS, et al. Single cell signaling pharmacodynamics in a phase 1b clinical trial of the axl inhibitor bemcentinib&nbsp;in acute myeloid leukemia and myelodysplastic syndrome. Presented at: 2019 EHA Congress; June 13-16, 2019; Amsterdam, Netherlands. Abstract PS999.
  4. BerGenbio presents preliminary phase II clinical data at EHA 24: bemcentinib in combination with low dose chemotherapy yields durable responses in AML patients unfit for intensive chemotherapy [news release]. Amsterdam, Netherlands: BerGenBio ASA; June 14, 2019. Accessed October 22, 2019.