RAS(ON) Inhibitors + Ivonescimab for Solid Tumors

This trial investigates a new treatment combination for adults with advanced or metastatic solid tumors that have a specific RAS mutation. The goal is to assess the safety, effectiveness, and behavior of this combination in the body. Participants will receive one of three experimental treatment combinations, each involving ivonescimab and a different RAS(ON) inhibitor (such as Zoldonrasib), possibly alongside other cancer drugs. Individuals with a confirmed RAS mutation who have not responded to or cannot tolerate standard treatments might be suitable for this study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Research has shown that combining Ivonescimab with RAS(ON) inhibitors like Daraxonrasib, Elironrasib, and Zoldonrasib is generally safe for patients. Previous studies found these combinations to have manageable safety profiles.

For Daraxonrasib with Ivonescimab, early trials showed positive safety results, allowing the treatment to progress to further testing, indicating it is safe enough for more study.

Elironrasib has updated safety data showing it is generally safe for patients with certain types of lung cancer.

Zoldonrasib, when combined with Ivonescimab, has been tested for safety and tolerability, although specific side effects are not detailed.

Researchers are excited about the treatments Ivonescimab and Zoldonrasib for solid tumors because they bring new mechanisms of action to the table. Unlike standard treatments that often target tumor growth with chemotherapy drugs, these investigational treatments work by inhibiting RAS(ON), a pathway known for driving cancer progression. Ivonescimab, in combination with various inhibitors, acts as a bispecific antibody, enhancing the immune system's ability to attack cancer cells. Meanwhile, Zoldonrasib specifically targets the mutant KRAS protein, a common culprit in many solid tumors, offering a more targeted therapy option. These unique approaches have the potential to improve outcomes where traditional therapies may fall short.

Research shows that RAS(ON) inhibitors like daraxonrasib, elironrasib, and zoldonrasib, when combined with ivonescimab, have promising effects against tumors with RAS mutations. In this trial, participants will join different treatment arms to receive these combinations. Arm A will explore daraxonrasib with ivonescimab, Arm B will investigate elironrasib with ivonescimab, and Arm C will study zoldonrasib with ivonescimab. Studies have found that ivonescimab, when combined with chemotherapy, can significantly slow tumor growth. Specifically, this combination improved the time lung cancer patients lived without their cancer worsening by 40%. Early results for elironrasib also show effectiveness against cancer cells with certain mutations. These findings suggest that these drug combinations might offer a new way to treat advanced cancers with RAS mutations.¹²³⁵⁶