Novel Agents for the Treatment of Melanoma

Source: OncLive, September 2019

Jeffrey S. Weber, MD, PhD: There’s a whole raft of phase III trials that will come to mature—SD-101, CMP-001, the MASTERKEY-265—and then there’s the NKTR-nivolumab trial. Jason, a lot of buzz about these IL-2–like compounds. There’s ALKS 4230, which is a genetically modified IL-2. There’s NKTR-214 which is a pegylated IL-2. And the idea was it would not bind to the alpha receptor of IL-2, so it wouldn’t promote T-regs [regulatory T-cells] and it would activate T-cells. What’s your read on the NKTR-214–nivolumab trial? That’s a phase III trial.

Jason J. Luke, MD, FACP: The predicate here being that before we had all these drugs we’ve just been discussing, a high-dose IL-2 was the therapy that was available to some patients and was associated with a long-term benefit. That’s really fallen away because of the toxicity, but we still all acknowledge the fact that some patients were cured. As you’re suggesting, these are novel approaches to harness IL-2 biology and then bring it into the checkpoint inhibitor space. NKTR-214 is a pegylated molecule that tries to sort of take the parts of the IL-2 molecule that we think are the important ones, then tries to use that in combination with checkpoint blockade to enhance that.

I think that the early data set are very interesting in that regard. The clinical data have showed that in some patients with advanced melanoma in the frontline setting, there were complete responders in patients who were PD-L1 [programmed death-ligand 1] negative, and that was thought to be pretty unlikely. There were changes on the translational level, in terms of number of immune cells going into tumors, and the immune changes in a tumor that you would think would associate with immune response. All that trended in the direction that you would expect, enough that this phase III trial has been launched.


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