Chung-Han Lee, MD, PhD: Ipilimumab is an anti-CTLA4 agent. While nivolumab is an anti—PD-1 agent, both of these checkpoint inhibitors work at different places within the immune system in activation. Anti-CTLA4 is an earlier event, while PD-1 really looks at immune exhaustion. Therefore, there is some preclinical rationale for synergism between them. As a result, these 2, in combination, will likely enhance each other’s effects beyond what is seen with single-agent PD-1 inhibition.

CheckMate 214 was a randomized phase III clinical trial of the combination of ipilimumab plus nivolumab versus sunitinib in first-line—treated patients. These included patients who were both intermediate- and poor-risk disease, as well as patients with favorable-risk disease. Within the intermediate- and poor-risk population, the outcomes were superior in comparison to Sutent (sunitinib)—from an objective response standpoint, a progression-free survival standpoint, and an overall survival standpoint. What was very interesting about that trial was that there also seemed to be some stratification between the intermediate- or poor-risk group versus the favorable-risk population. In the favorable-risk population, we actually saw the reverse effect, in which patients who got single-agent sunitinib seemed to do better than with the combination checkpoint inhibitor regimen.

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