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Cited by 237Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)

Diab, Adi, Tannir, Nizar M., Bentebibel, Salah-Eddine, Hwu, Patrick, Papadimitrakopoulou, Vassiliki, Haymaker, Cara, Kluger, Harriet M., Gettinger, Scott N. +15 more·2020·Cancer Discovery
DOI 10.1158/2159-8290.cd-19-1510

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Abstract

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-naïve 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. See related commentary by Rouanne et al., p. 1097. This article is highlighted in the In This Issue feature, p. 1079

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Crossref · 10.1158/2159-8290.cd-19-1510

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7 of 7 references verified0 citation errors · 0 not checkable

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  • Bempegaldesleukin is associated with increased proliferation and activation of tumor-infiltrating lymphocytes among patients with solid tumors.

    “Bempegaldesleukin, a CD122-preferential IL-2 pathway agonist, is associated with increased proliferation and activation of TILs among patients with solid tumors [163].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [163]

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Authors
Diab, A., Tannir, N. M., Bentebibel, S.-E., Hwu, P., Papadimitrakopoulou, V., Haymaker, C., Kluger, H. M., Gettinger, S. N., Sznol, M., Tykodi, S. S., Curti, B. D., Tagliaferri, M. A., Zalevsky, J., Hannah, A. L., Hoch, U., Aung, S., Fanton, C., Rizwan, A., Iacucci, E., Liao, Y., Bernatchez, C., Hurwitz, M. E., & Cho, D. C.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Yale University (US)
  • University of Washington (US)
  • 4Providence Cancer Center and Earle A. Chiles Research Institute, Portland, Oregon.
  • Nektar Therapeutics (United States) (US)
  • NYU Langone Health (US)
ORCID
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2020-08-01
Volume
10
Issue
8
Pages
1158-1173
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-19-1510
OpenAlex
W3026452138
Cited by
237
References
7
Citations by year
2026: 14 · 2025: 24 · 2024: 31 · 2023: 27 · 2022: 54 · 2021: 67 · 2020: 18 · 2015: 1
FWCI
15.07
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
NKTR-214, nivolumab, CD122, PD-1/PD-L1 blockade, immune checkpoint inhibitors, combination immunotherapy, advanced solid tumors, melanoma, renal cell carcinoma, non-small cell lung cancer, CD8+ T cell infiltration, tumor-infiltrating lymphocytes, PD-L1 expression, dose-limiting toxicity, objective response rate
MeSH terms
Antineoplastic Agents, Immunological, Nivolumab, Immune Checkpoint Inhibitors, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Female, Humans, Immunotherapy, Interleukin-2, Kidney Neoplasms, Lung Neoplasms, Male, Melanoma, Middle Aged, Polyethylene Glycols, Gene Expression Regulation, Neoplastic, Lymphocytes, Tumor-Infiltrating, Treatment Outcome, Lymphocyte Count, Young Adult, Programmed Cell Death 1 Receptor

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