James Larkin, MD, PhD, of the Royal Marsden NHS Foundation Trust, London, UK, discusses the next steps for the treatment of advanced melanoma. Dr Larkin first discusses that it really comes back down to the patients who are not benefiting from the use of checkpoint inhibitors such as nivolumab and pembrolizumab. He highlights that a lot of the interest in this situation lies with figuring out what is inside of the tumor which stops the drug from carrying out its full effect. He believes that in cases of clinical trials, when the drug alone is not working, a biopsy should be carried out, and the initial drug should then be partnered up with another suitable drug, in attempt to get round cases of resistance. Dr Larkin further explains that there are numerous numbers of immune checkpoints on T-cells. There are drugs that target CTLA-4, and drugs that target PD-1 and there are many other targets and drugs. He believes that there will not be a ‘one size fits all’ approach for patients who are not responding, and that it may be the case of needing to individualize each case for patients. Recorded at the American Society of Oncology (ASCO) 2016 Annual Meeting held in Chicago, IL.