Journal
CANCER DISCOVERY
Volume 10, Issue 8, Pages 1158-1173Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-19-1510
Keywords
-
Categories
Funding
- Translational Molecular Pathology-Immunoprofiling Laboratory (TMP-IL) at the Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center (Houston, TX)
- Nektar Therapeutics
Ask authors/readers for more resources
This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempegaldesleukin (NKTR-214/BEMPEG). a CD122-preferential IL2 pathway agonist, plus nivolumab in 38 patients with selected immunotherapy-naive advanced solid tumors (melanoma. renal cell carcinoma, and non-small cell lung cancer). Three dose-limiting toxicities were reported in 2 of 17 patients during dose escalation [hypotension (n=1), hyperglycemia (n= 1), metabolic acidosis (n=1)]. The most common treatment-related adverse events (TRAE) were flu-like symptoms (86.8%), rash (78.9%), fatigue (73.7%), and pruritus (52.6%). Eight patients (21.1%) experienced grade 3/4 TRAEs: there were no treatment-related deaths. Total objective response rate across tumor types and dose cohorts was 59.5% (22/37), with 7 complete responses (18.9%). Cellular and gene expression analysis of longitudinal tumor biopsies revealed increased infiltration, activation, and cytotoxicity of CD8(+) T cells, without regulatory T-cell enhancement. At the recommended phase II dose. BEMPEG 0.006 mg/kg plus nivolumab 360 mg every 3 weeks, the combination was well tolerated and demonstrated encouraging clinical activity irrespective of baseline PD-L1 status. SIGNIFICANCE. These data show that BEMPEG can be successfully combined with a checkpoint inhibitor as dual immunotherapy for a range of advanced solid tumors. Efficacy was observed regardless of baseline PD-L1 status and baseline levels of tumor-infiltrating lymphocytes, suggesting therapeutic potential for patients with poor prognostic risk factors for response to PD-1/PD-L1 blockade.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available