Circulating Tumour DNA Guided Adaptive BRAF and MEK Inhibitor Therapy

Encorafenib and binimetinib given in combination ("the treatment") is a standard of care treatment in the UK for late stage cutaneous melanoma, a skin cancer that starts in the cells that produce skin pigmentation. 'Late stage' means it can't be surgically removed, or has spread. The treatment is taken daily. Resistance to the treatment can develop after about 12-15 months. During this period, the treatment will kill the less resistant cells, meaning the tumour has a greater proportion of cells that are resistant to the treatment. This study aims to investigate if the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour as a whole less resistant to the treatment, and increasing the time it takes for the disease to progress. A blood test that measures the amount of tumour DNA circulating in the patient's blood (known as ctDNA) will be conducted every two weeks to check if the cancer cells are still present, and if they are becoming active. The result of this test will allow doctors to monitor the activity of the tumour and judge when to pause and resume treatment. This intermittent treatment is called 'adaptive therapy'. The investigators intend to recruit 40 participants with late stage cutaneous melanoma from NHS hospitals in the UK. Ten will receive the standard, daily treatment, and thirty will receive adaptive therapy. Patients will receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first. As well as the fortnightly visits to hospital, patients will required to complete EORTC QLQ-C30 and PRO-CTCAE questionnaires in order for their quality of life to be assessed. These will be completed before their treatment starts; every 12 weeks from when they start treatment; and again if their cancer progresses.