Rituximab + Hyaluronidase with Immunotherapy for Melanoma

This trial explores whether adding rituximab (an antibody therapy) and hyaluronidase to the usual treatment can help prevent side effects in individuals with advanced melanoma (a type of skin cancer) that cannot be surgically removed. Participants will receive standard immune therapy with ipilimumab (Yervoy) and nivolumab (Opdivo). Some participants will also receive rituximab and hyaluronidase to determine if it makes a difference. The trial seeks participants with stage III-IV melanoma who have not received similar immune therapies in the past year and are ready for immune checkpoint therapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

The trial does not specify if you need to stop taking your current medications, but you cannot be on corticosteroid therapy unless it's for adrenal insufficiency or occasional use like inhalers or nasal sprays. It's best to discuss your specific medications with the trial team.

Research shows that using rituximab and hyaluronidase together is generally safe for patients. One study found that starting with rituximab given intravenously (IV) and then switching to subcutaneous doses did not cause any unexpected side effects, indicating predictable safety for this combination.

For ipilimumab and nivolumab, treatments that help the immune system fight cancer, studies have shown they can cause immune-related side effects. These treatments boost the immune system to attack cancer, but they can also affect healthy cells. Common side effects include skin rash and fatigue, while less common but more serious issues include liver inflammation.

Researchers are excited about combining Rituximab and hyaluronidase with immunotherapy for melanoma because it introduces a novel approach to treatment. Unlike the standard care, which primarily uses ipilimumab and nivolumab to stimulate the immune system against cancer cells, this approach adds Rituximab, an antibody that targets specific proteins on cancer cells, potentially enhancing the immune response. Additionally, the use of hyaluronidase allows for easier and faster subcutaneous administration of Rituximab, making the treatment more convenient and potentially improving patient compliance. This combination aims to improve the effectiveness and efficiency of melanoma treatment by targeting cancer in multiple ways.

Studies have shown that combining rituximab with chemotherapy can provide long-term benefits, such as delaying cancer progression. Research suggests rituximab, commonly used for immune-related conditions, might lessen side effects from immunotherapy. In past studies, rituximab proved effective for patients with chronic immune disorders, indicating potential benefits for similar issues in melanoma treatment. While researchers continue to study its exact effects on melanoma, early findings suggest it could help manage immune-related challenges during treatment. This trial tests the combination of rituximab and hyaluronidase in one treatment arm to determine if it can better support patients receiving standard melanoma treatments like ipilimumab and nivolumab.³⁶⁷⁸⁹