TY - JOUR
T1 - Bempegaldesleukin (NKTR-214) plus nivolumab in patients with advanced solid tumors
T2 - Phase I dose-escalation study of safety, effi cacy, and immune activation (PIVOT-02)
AU - Diab, Adi
AU - Tannir, Nizar M.
AU - Bentebibel, Salah Eddine
AU - Hwu, Patrick
AU - Papadimitrakopoulou, Vassiliki
AU - Haymaker, Cara
AU - Kluger, Harriet M.
AU - Gettinger, Scott N.
AU - Sznol, Mario
AU - Tykodi, Scott S.
AU - Curti, Brendan D.
AU - Tagliaferri, Mary A.
AU - Zalevsky, Jonathan
AU - Hannah, Alison L.
AU - Hoch, Ute
AU - Aung, Sandra
AU - Fanton, Christie
AU - Rizwan, Ahsan
AU - Iacucci, Ernesto
AU - Liao, Yijie
AU - Bernatchez, Chantale
AU - Hurwitz, Michael E.
AU - Cho, Daniel C.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/8
Y1 - 2020/8
N2 - This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempega ldesleukin (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 fl u-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 infi ltration, 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. Effi cacy was observed regardless of baseline PD-L1 status and baseline levels of tumor-infi ltrating lymphocytes, suggesting therapeutic potential for patients with poor prognostic risk factors for response to PD-1/PD-L1 blockade.
AB - This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempega ldesleukin (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 fl u-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 infi ltration, 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. Effi cacy was observed regardless of baseline PD-L1 status and baseline levels of tumor-infi ltrating lymphocytes, suggesting therapeutic potential for patients with poor prognostic risk factors for response to PD-1/PD-L1 blockade.
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U2 - 10.1158/2159-8290.CD-19-1510
DO - 10.1158/2159-8290.CD-19-1510
M3 - Article
C2 - 32439653
AN - SCOPUS:85089129150
SN - 2159-8274
VL - 10
SP - 1158
EP - 1173
JO - Cancer discovery
JF - Cancer discovery
IS - 8
ER -