The following commentary by our CEO, Dr. Frank Borriello, is about the current challenges and limitations of immune checkpoint inhibitor (ICI) combinations in cancer treatment. Dr. Borriello touches on the need for a strategic shift in approach.

This article – published in Endpoints – highlights issues that go beyond the failure of a single trial to meet its pre-specified endpoint.

There is no doubt that immune checkpoint inhibitors (ICIs) represent a major breakthrough in demonstrating the critical role of the immune system in combating cancer. However, despite their blockbuster status, ICIs are effective in only a minority of patients and are associated with significant side effects.

Recent clinical studies evaluating combinations of ICIs have largely failed to show improved efficacy, indicating that while this mechanism is crucial, it has inherent limitations. Key observations from these studies include:

• The primary ICI pathways may have already been identified
• Additional pathways may be physiologically constrained in their impact
• If resources were infinite, one could continue combining ICIs in hopes of discovering an exceptional combination, but this approach is not practical

Given the reality of finite resources, we believe it is more practical to combine agents with demonstrated single-agent clinical activity and complementary mechanisms of action—an established and successful strategy in oncology.

At Alloplex, we have shown that our SUPLEXA therapeutic cells exhibit single-agent activity in end-stage cancer patients and possess mechanisms that should complement the mode of action of ICIs. We are eager to test this hypothesis in clinical trials.