Bemcentinib is an investigational oral drug that functions as a first-in-class AXL inhibitor. It is being explored for its potential therapeutic effects across various medical conditions, primarily in oncology. Researchers are examining its influence on disease progression, both as a single agent and in combination with other treatments.
How Bemcentinib Works
Bemcentinib inhibits the activity of the AXL receptor tyrosine kinase. AXL is a cell membrane receptor involved in cellular signaling pathways, influencing cell proliferation, survival, and migration. AXL activation occurs when its natural ligand, Growth Arrest-specific 6 (GAS6), binds to it, leading to downstream signaling.
Increased AXL function has been linked to drug resistance and immune evasion by tumor cells, potentially leading to more aggressive cancers. By inhibiting AXL, bemcentinib may exert anti-tumor and anti-inflammatory effects. AXL also promotes cell survival.
Conditions Under Investigation for Bemcentinib
Bemcentinib is being investigated for various conditions, particularly certain types of cancer. It is being studied in clinical trials for non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), triple-negative breast cancer (TNBC), melanoma, and metastatic pancreatic cancer. AXL is often overexpressed in these cancer types, which is associated with a less favorable prognosis and resistance to existing therapies.
In non-small cell lung cancer, bemcentinib is being evaluated in combination with standard treatments. AXL expression is a negative prognostic factor in NSCLC. AXL inhibition has shown potential to enhance the effectiveness of immune checkpoint inhibitors, particularly in patients with STK11 mutations.
For acute myeloid leukemia and myelodysplastic syndromes, bemcentinib has been explored as a targeted therapy, especially for patients who have relapsed or are refractory to prior treatments. AXL is upregulated on leukemic stem cells in both AML and MDS. Clinical trials have evaluated bemcentinib’s safety and efficacy in these patient populations.
Beyond cancer, bemcentinib has also been investigated for respiratory infections, including COVID-19. It can inhibit SARS-CoV-2 host cell entry and promote anti-viral responses. It has also shown activity against Respiratory Syncytial Virus (RSV), influenza, and rhinovirus by reducing inflammatory cytokines.
Research and Clinical Development
Bemcentinib has progressed through various stages of clinical trials, primarily in Phase II for a range of solid and hematological tumors. It has been tested as a monotherapy and in combination with other treatments, including immunotherapy, chemotherapy, and targeted therapeutics.
In non-small cell lung cancer, a Phase II study combining bemcentinib with pembrolizumab in recurrent NSCLC patients showed promising preliminary data. Another Phase Ib/IIa trial is evaluating bemcentinib with pembrolizumab and platinum doublet chemotherapy as a first-line treatment for NSCLC patients with STK11 mutations, a subgroup often showing poorer response to existing therapies.
For acute myeloid leukemia and myelodysplastic syndromes, a Phase Ib/II study has evaluated bemcentinib as a single agent or in combination with other treatments. Final results from a Phase II study indicated that bemcentinib was well tolerated and showed durable responses.
In the context of COVID-19, bemcentinib was selected for a Phase II clinical trial. Data from this randomized study suggested that bemcentinib could increase the rate of ventilator-free survival in hospitalized COVID-19 patients.
Potential Considerations
Bemcentinib is an investigational drug not yet approved for general use. Potential considerations include observed side effects. Common adverse reactions reported in clinical trials have included fatigue, nausea, and diarrhea.
Some patients in trials have also experienced neutropenia, a decrease in a type of white blood cell. Other less common side effects have also been reported. Healthcare professionals closely monitor patients during trials to manage these potential effects. Individuals should always consult with a qualified healthcare professional for medical advice regarding any health concerns or potential treatments.