Promising early results with imneskibart, low-dose subcutaneous IL-2, and nivolumab in patients who do not respond to or who relapse after receiving combination checkpoint inhibitors

Early data for imneskibart with aldesleukin presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago support a future treatment option for patients who initially do not respond to checkpoint inhibitors or who later relapse. Unfortunately, there are limited options for these patients. Lifileucel TIL therapy is currently the only FDA-approved product specifically approved for patients who do not respond to—or whose response is not durable with—checkpoint inhibitors. 

Imneskibart is a human IgG1 monoclonal antibody designed with artificial intelligence that works differently from other IL-2 therapies. IL-2 is a type of chemical messenger (cytokine) that the body normally produces to manage and stimulate the immune system. Human IgG1 monoclonal antibody cancer therapies are versions of your body’s natural antibodies made in the lab. They attach to specific targets on tumor cells and block dangerous growth signals or flag cancer cells so your immune system can destroy them. Imneskibart was designed to have beneficial effects on the immune system and not have the negative adverse effects of IL-2 therapy that have been seen in the past.  

Patients in this Phase 1/2 study had metastatic melanoma whose disease progressed after receiving standard checkpoint inhibitor therapies such as ipilimumab (Yervoy) plus nivolumab or the combination therapy nivolumab/relatlimab (Opdualag).  

In this study, the objective response rate (the percentage of patients in a treatment group whose cancer shrinks or disappears) was 33%. In total, 4 out of 12 patients had partial responses (meaning that the tumor size decreased) and 4 out of 12 patients had stable disease (tumor growth did not shrink enough to be a partial response and growth did not progress). The disease control rate (the combination of responses and stable disease) was 67%.  

Most adverse events were mild or moderate in severity and were manageable, and no patients discontinued treatment due to an adverse event. Patients did experience fever and chills seen with other IL-2 therapies, but they were not severe, and patients did not experience life-threatening hypotension (very low blood pressure). The treatment was able to be administered in an outpatient setting without any mandatory hospital admissions that have been required with other IL-2 therapies.