An estimated 40-50% of patients with metastatic melanoma experience resistance checkpoint inhibitors and get little to no benefit from ipilimumab, pembrolizumab, or nivolumab.
Of the 50-60% of patients who respond initially, approximate 30% experience progression over time, therefore approximately 15% of patients overall with metastatic disease end up with secondary resistance at some point.
Secondary resistance includes responders who progress while on treatment and responders his disease progresses at some point after they stop check point inhibitor treatment.
Among patients who initially respond to checkpoint inhibitors but develop aggression after treatment ends, approximately 15-30% they respond to a second course.
Patients with high levels of LDH have a lower chance of responding to checkpoint inhibitors, but some do gain substantial benefit.
PD-L 1 negative patients still may benefit from anti-PD-1 therapy or from combination of Ipilimumab and Nivolumab.
Almost all patients who do not respond to Ipilimumab and Nivolumab by 12 weeks are not going to respond.
Targeting lymphocyte activation gene 3 (LAG-3) a cell surface protein eXpressed on immune cells where it negatively regulates cell proliferation and effector function, with relatinib, when added to Nivolumab demonstrated increased activity compared toNivolumab alone in patients with treatment naïve metastatic melanomas.