PIVOT-02: Implications and Next Steps in Research

Adi Diab, MD:I think we established a few things from the PIVOT-02 study. The combination of NKTR-214 as cytokine to harness the IL-2 [interleukin-2] pathway with nivolumab (Opdivo) remains safe. The regimen is tolerable and can be administered in the outpatient setting with good safety. That’s very important. This is the first time you can administer a cytokine that harnesses the IL-2 pathway in conjunction with a checkpoint inhibitor in the outpatient setting. In terms of efficacy, this combination mediates meaningful responses—a 53% overall response rate and a 24% complete response rate. These are meaningful responses that suggest that this is an additive or synergistic effect, and this should be evaluated in a randomized phase III trial against the standard of care.

The biomarker data further reinforce that there is an additive or a synergistic effect of this combination because we see proliferation of T cells. We see clear activation of the IL-2 pathway that leads to activation of T cells, proliferation of T cells, and possible proliferation of antigens and experienced T cells. We see that in the blood but also in the tumor microenvironment. What is interesting is that we see a new trafficking of T cells to the tumor microenvironment, which we think is mediated by NKTR-214. I think that theoretically increases the chances for an immune-mediated anti-cancer response.

In terms of the combination regimen, this data were supportive enough to launch a phase III randomized clinical trial of NKTR-214 against the standard of care, which in this case is nivolumab. We will have to wait to see what the results of this trial are. The phase III trial has launched, and we will see how this develops. NKTR-214 will be evaluated alone as well as with a checkpoint inhibitor in patients who are refractory to checkpoint inhibitors. That needs to be looked at more in a larger number of patients. We are also looking to see how to incorporate NKTR-214 as a cytokine and a growth factor for T cells with other combinations, such as with intratumoral TLRs [toll-like receptors] 7 and 8. We are excited about looking into how the combination of NKTR-214 as a cytokine will complement intratumoral TLR7/8, and we will be evaluating the efficacy and the safety of this combination in the REVEAL trial.

Transcript edited for clarity.