Abstract 3265: NKTR-255, a polymer-conjugated IL-15 enhances anti-tumor NK cell responses and synergizes with monoclonal antibodies to provide long-term survival in human lymphoma model

Miyazaki, Tsuyoshi; Kivimäe, Saul; Pena, Rhoneil; Kuo, Peiwen; Hennessy, Marlene; Addepalli, Murali; Dixit, Neha; Nieves, Wildaliz; Sheibani, Sara; Maiti, Mekhala; VanderVeen, Laurie A.; Wilczek, Joanna; Madakamutil, Loui; Zalevsky, Jonathan

doi:10.1158/1538-7445.sabcs18-3265

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“…Therefore, studies have been carried out to evaluate whether NKTR-255 can enhance tumor-directed mAb activity in preclinical cancer models, including MM, lymphoma and solid tumors. In an MM cell line, NKTR-255 boosted NK cell proliferation and activation that translated into enhanced daratumumab-mediated in vitro ADCC [31]. Furthermore, in a Daudi B-cell lymphoma mouse model, NKTR-255 combined with daratumumab or rituximab prolonged the survival of treated animals compared with single-agent treatment [31].…”

Section: Nktr-255mentioning

confidence: 98%

“…In an MM cell line, NKTR-255 boosted NK cell proliferation and activation that translated into enhanced daratumumab-mediated in vitro ADCC [31]. Furthermore, in a Daudi B-cell lymphoma mouse model, NKTR-255 combined with daratumumab or rituximab prolonged the survival of treated animals compared with single-agent treatment [31]. These observations were extended further in human tumor xenograft models in which NKTR-255 combined with cetuximab induced NK cell expansion and increased functional activation, as well as delayed or inhibited tumor growth [32].…”

Section: Nktr-255mentioning

confidence: 99%

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Phase I Study Protocol: NKTR-255 as Monotherapy or Combined with Daratumumab or Rituximab in Hematologic Malignancies

et al. 2021

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NKTR-255 is an investigational polyethylene glycol-modified recombinant human IL-15 (rhIL-15) receptor agonist, designed to improve the immunotherapeutic and anti-cancer benefit observed with rhIL-15 while circumventing the toxicities associated with this therapy. In preclinical studies, NKTR-255 has demonstrated enhanced proliferation and function of CD8+ T cells and natural killer cells, as well as enhanced anti-tumor activity and survival both as monotherapy and in combination with monoclonal antibodies in multiple cancer models. Here, we describe the rationale and design of the first-in-human Phase I, dose-escalation and dose-expansion study of NKTR-255 alone and in combination with daratumumab or rituximab in adults with relapsed/refractory multiple myeloma or non-Hodgkin's lymphoma that will determine the maximum tolerated dose and recommended Phase II dose for NKTR-255.

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Section: Nktr-255mentioning

confidence: 98%

Section: Nktr-255mentioning

confidence: 99%