Melanoma is the most serious type of skin cancer
Melanoma occurs when the pigment cells in the skin (melanocytes), divide uncontrollably. It is estimated that in 2016, there were almost 150,000 melanoma diagnoses in the US alone. If detected very early, melanoma has a good prognosis: for patients with advanced melanoma, however, the probability of surviving five or more years is less than 20%.
Systemic treatment options for advanced melanoma depend on the presence or absence of driver mutations and the overall tumour burden. Broadly speaking, metastatic melanoma patients receive either
- an immune checkpoint inhibitor like KEYTRUDA or
- targeted therapy against the relatively common BRAF mutation like the drug combination TAFINLAR/MEKINIST.
The orally available, selective AXL inhibition shows promise enhancing the efficacy treatments across the melanoma therapy landscape
Long lasting responses and cures have been reported for immune therapy in melanoma however up to half of the patients receiving KEYTRUDA monotherapy do not respond to treatment. Although response rates to targeted therapy are usually rapid and strong, virtually all patients develop resistance to targeted inhibitors like TAFINLAR/MEKINIST over time. Thus, agents to improve outcome are urgently needed.
There is a strong rationale for AXL inhibition to improve the efficacy of immune checkpoint inhibitor and targeted therapy in melanoma:
- AXL up-regulation has been implicated in melanoma progression and resistance to BRAF pathway inhibition
- AXL is upregulated in patients resistant to immune checkpoint inhibition
- AXL inhibition via bemcentinib shows pre-clinical efficacy in melanoma cells.