Nivolumab + Relatlimab + Ipilimumab for Melanoma

This trial tests a combination of three treatments—Nivolumab, Relatlimab, and Ipilimumab, all immunotherapy drugs—to determine the best dose and assess their safety and effectiveness against advanced melanoma, a serious type of skin cancer. The researchers aim to discover if this combination can manage the disease better than current treatments. Participants should have advanced melanoma that has not been treated with systemic therapy before. This trial might suit those diagnosed with stage III or IV melanoma who have not undergone specific prior treatments. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in melanoma treatment.

The trial protocol does not specify if you must stop taking your current medications. However, the use of corticosteroids is not allowed for 14 days before starting the trial, except for certain cases like physiological replacement. It's best to discuss your specific medications with the trial team.

Previous studies found the combination of nivolumab and relatlimab to be safe, with side effects that doctors expected based on past experiences. However, adding ipilimumab to nivolumab can cause more immune-related side effects, such as skin rashes or liver problems, which are common in treatments that boost the immune system.

Using relatlimab with nivolumab increases the risk of heart-related issues compared to nivolumab alone. While these drugs can effectively treat melanoma, they may also cause side effects that require monitoring.

Researchers are excited about the combination of Nivolumab, Relatlimab, and Ipilimumab for melanoma because it introduces a novel approach by targeting different immune checkpoints simultaneously. Unlike the standard treatments that typically involve single-agent immunotherapies like Nivolumab or Ipilimumab, this combination leverages Relatlimab to target the LAG-3 protein, in addition to the PD-1 and CTLA-4 pathways. This multi-targeted strategy could potentially enhance the immune system's ability to fight melanoma more effectively and may lead to improved outcomes for patients who have limited options with current therapies.

Studies have shown that using nivolumab and ipilimumab together treats advanced melanoma more effectively than using each drug alone. Research also suggests that adding relatlimab to nivolumab works as well as the combination of ipilimumab and nivolumab. In this trial, participants will receive the combination of nivolumab, relatlimab, and ipilimumab. This combination has shown promising results, with some studies reporting that up to 56% of patients respond positively. For patients with advanced melanoma, these treatments have extended survival without disease progression. Overall, these drugs enhance the immune system's ability to fight cancer cells.¹³⁴⁶⁷