Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies

Future Oncol. 2021 Sep;17(27):3549-3560. doi: 10.2217/fon-2021-0576. Epub 2021 Jun 22.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT04136756.

Keywords: IL-15; NKTR-255; daratumumab; multiple myeloma; non-Hodgkin lymphoma; rituximab; study protocol.

Plain language summary

Lay abstract Interleukin-15 (IL-15) is a protein that helps the body's natural immune system to defend itself against infections and diseases like cancer. This article discusses a clinical trial in patients with multiple myeloma or non-Hodgkin's lymphoma that evaluates a new investigational medicine, NKTR-255, a polymer-modified form of IL-15 that has been engineered to improve its ability to provide a sustained anti-tumor immune response. The trial will explore different doses of NKTR-255 to determine patient side effects and to find the highest acceptable dose that patients can tolerate. Based on this, a dose will be chosen that offers an optimal balance between having a positive anti-cancer effect and minimizing side effects. This dose will be tested further in patients who have had different treatments in the past. If the side effects are acceptable, this dose will be tested in a new trial in a large number of patients. Clinical Trial Registration: NCT04136756 (ClinicalTrials.gov).

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Drug Therapy, Combination
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Interleukin-15 / chemistry
  • Interleukin-15 / therapeutic use*
  • Polyethylene Glycols / chemistry
  • Rituximab / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Interleukin-15
  • Polyethylene Glycols
  • Rituximab
  • daratumumab

Associated data

  • ClinicalTrials.gov/NCT04136756

Grant support