Novel Immunotherapy Combination Active in Metastatic Melanoma
Posted: Monday, July 22, 2019
The combination of bempegaldesleukin (NKTR-214), a CD122-preferential interleukin-2 pathway agonist, and the PD-1 inhibitor nivolumab as first-line treatment in patients with metastatic melanoma produced a 34% complete response rate at a 12-month follow-up analysis. Additionally, new baseline biomarker analyses identified baseline immune signatures that appear to correlate with response in patients with melanoma. These efficacy and safety results from the ongoing PIVOT-02 trial were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 2623).
“The response rates observed in both the favorable and unfavorable tumor microenvironments indicate the potential of this combination and support its broad development,” concluded Michael E. Hurwitz, MD, PhD, of Yale School of Medicine, New Haven, Connecticut, and colleagues.
Patients with metastatic melanoma received NKTR-214 plus nivolumab as first-line therapy in this phase II study. At a median follow-up of 12.7 months, the confirmed objective response rate in 38 efficacy-evaluable patients was 53%. A maximum reduction of 100% in target lesions was achieved in 16 patients (42%).
In the exploratory biomarker analyses, patients were divided into high- and low-biomarker subgroups based on their pretreatment tumor-infiltrating lymphocyte levels. High and low interferon-gamma gene scores correlated with a response rate of 67% and 20%, respectively. High and low CD3-tumor-infiltrating lymphocyte levels were associated with response rates of 79% and 29%; patients with PD-L1–positive and PD-L1–negative disease achieved a response rate of 68% and 43%, respectively. It is important to note that the responses were observed in some patients with the least favorable tumor microenvironment—characterized as both PD-L1–negative and low tumor-infiltrating lymphocyte levels—with responses of 17% (low CD8 tumor-infiltrating lymphocyte levels) and 25% (low CD3 tumo- infiltrating lymphocyte levels), respectively.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.