Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

This study is testing a combination of low-dose metronomic cyclophosphamide (a chemotherapy drug given regularly in small amounts) with pembrolizumab (an immunotherapy drug) in people with advanced melanoma (skin cancer) that has stopped responding to standard immune checkpoint inhibitor treatments. **You may be eligible if...** - You are 18 or older with advanced melanoma (Stage III or IV, non-ocular) that cannot be surgically removed - Your melanoma has progressed or stopped responding to prior checkpoint immunotherapy drugs - You have measurable disease on imaging - Your general health and organ function are adequate **You may NOT be eligible if...** - You have ocular (eye-related) or uveal melanoma - You have another active cancer (with some exceptions for cancers treated and in remission) - You are pregnant or breastfeeding - You have active autoimmune disease requiring systemic treatment - You have severe heart, liver, or lung conditions Talk to your doctor to see if this trial is right for you.