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Selective AXL inhibitors

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Home  /  Pipeline  /  bemcentinib | Melanoma

bemcentinib | Melanoma

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.

It is estimated that more than 250,000 new cases will be diagnosed in the US in 2018. 20% of breast cancers lack receptors for three common hormones (oestrogen, progesterone and HER2) and are thus called triple-negative breast cancers (TNBC).

Treatment options for TNBC are limited to intense chemotherapy, but disease recurrence is frequent and aggressive. Consequently, novel treatment strategies for TNBC 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.
  • Phase II bemcentinib combination trial in melanoma

    Up to 92 patients will be randomised to receive KEYTRUDA or TAFINLAR/MEKINIST alone or in combination with bemcentinib.

    Clinical Trial Melanoma
    Scientific poster presentations

    ASCO 2018World Congress Melanoma 2017

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