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Updated: Jan 26, 2026

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A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced

Salah-Eddine Bentebibel1, Michael E Hurwitz2, Chantale Bernatchez1

  • 1The University of Texas MD Anderson Cancer Center, Houston, Texas.

Cancer Discovery
|April 17, 2019
PubMed

Insights

NKTR-214 (bempegaldesleukin), an IL2 pathway agonist, demonstrated safety and clinical activity in a phase I study. It effectively activated immune cells and reduced tumors without expanding regulatory T cells.

Area of Science:

  • Oncology
  • Immunotherapy
  • Pharmacology

Background:

  • NKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist engineered for sustained IL2 receptor signaling.
  • It aims to enhance CD8+ T and natural killer cell activation while minimizing regulatory T cell (Treg) expansion in the tumor microenvironment.

Purpose of the Study:

  • To evaluate the safety, tolerability, and preliminary clinical activity of NKTR-214 in a first-in-human phase I study.
  • To determine the recommended Phase II dose (RP2D) for NKTR-214.

Main Methods:

  • A multicenter, first-in-human, phase I study of NKTR-214 administered in an outpatient setting.
  • Assessment of safety, pharmacodynamics (immune cell activation, Treg levels), and clinical activity (tumor response, disease stabilization) through peripheral blood analysis and on-treatment tumor biopsies.
  • Transcriptional analysis of tumor biopsies to evaluate IL2 pathway engagement and effector gene expression.

Main Results:

  • NKTR-214 was well tolerated and showed clinical activity, including tumor shrinkage and durable disease stabilization in heavily pretreated patients.
  • Observed immune activation and increased immune cell numbers in peripheral blood across all doses, with sustained activity upon repeated administration.
  • On-treatment biopsies confirmed NKTR-214 promoted immune cell increases with limited Treg expansion, and transcriptional analysis indicated IL2 pathway engagement and increased effector gene expression.

Conclusions:

  • NKTR-214 is a well-tolerated IL2 pathway agonist with demonstrated clinical activity and favorable immunomodulatory effects.
  • The recommended Phase II dose of NKTR-214 is 0.006 mg/kg every three weeks.
  • NKTR-214 shows promise as a key component in immunotherapy treatment algorithms, particularly in combination with agents like checkpoint inhibitors.

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