A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors.

Abstract

e14040 Background: NKTR-214 is a CD-122-biased agonist that targets the IL-2 pathway and is designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβɣ) to preferentially activate and expand NK and effector CD8+ T cells over T regulatory cells within the tumor microenvironment. In a phase 1 monotherapy trial, pts treated with NKTR-214 demonstrated a substantial increase in CD8+ T and NK cells within the tumor microenvironment even when pretreated with multiple prior immunotherapeutic agents (abstract submitted). Based on this biomarker data and a favorable safety profile, a trial combining NKTR-214 and nivolumab was initiated. Methods: This is an on-going phase 1/2 study of NKTR-214 plus nivolumab in Pts with either melanoma (Mel), NSCLC, renal, bladder, or TNBC. Pts who are immunotherapy naïve or checkpoint therapy relapse/refractory are being studied separately. NKTR-214 and nivolumab are administered IV on a q2w or q3w schedule. Cohort 1 received NKTR-214 0.006 mg/kg q3w with nivolumab 240 mg q2w. Blood and tumor tissue were collected to measure immune activation using flow cytometry, immunohistochemistry, T cell clonality and gene expression analyses. Results: As of February 7, 2017, 5 Pts have been treated with the combination and all Pts were naïve to checkpoint inhibitors. There have been no dose limiting toxicities, no drug-related or immune related grade 3-5 adverse events (TRAEs) and no Pts have discontinued treatment. The most common TRAEs were pruritis and rash. Radiographic scans were available for 2 Pts. On treatment, Pt 1 with Mel had a mixed radiographic response at 1st scan, a ~40% decrease in LDH and a robust tumor immune cell infiltrate at week 3 the majority being newly proliferating CD8+ T cells expressing PD-1. Pt 2 with Mel had an unconfirmed complete response per RECIST 1.1 after 6 weeks of treatment; follow up tumor response data will be presented. Conclusions: Preliminary data demonstrate that NKTR-214 and nivolumab combination therapy is well tolerated with early evidence of clinical activity. Updated safety, pharmacokinetics, tumor response and biomarker data will be presented. Clinical trial information: NCT02983045.