Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors

J Immunother Cancer. 2024 May 3;12(5):e008847. doi: 10.1136/jitc-2024-008847.

Abstract

Patients with advanced cancer, previously treated with immune checkpoint blockade therapy, may retain residual treatment when undergoing the initial infusion of experimental monotherapy in phase 1 clinical trials. ANV419, an antibody-cytokine fusion protein, combines interleukin-2 (IL-2) with an anti-IL-2 monoclonal antibody, aiming to stimulate the expansion of CD8 T and natural killer lymphocytes while restricting regulatory T lymphocytes. In the recent publication of the phase 1 dose escalation study of ANV419, a notable gap exists in detailed information regarding patients' prior antitumoral treatments, specifically programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) targeted monoclonal antibodies. Some patients likely retained residual anti-PD-1/PD-L1 monoclonal antibodies, potentially influencing the outcomes of ANV419. In a separate clinical cohort, we retrospectively measured the residual concentration of nivolumab and pembrolizumab, revealing persistent serum concentrations of anti-PD-1/PD-L1 antibodies even months after treatment cessation. This underscores the importance of comprehensively documenting prior immunotherapy details in clinical trials. Such information is crucial for understanding potential interactions that may impact both immunological and clinical effects.

Keywords: Immune Checkpoint Inhibitor; Pharmacodynamics - PD; Pharmacokinetics - PK.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / therapeutic use

Substances

  • Interleukin-2
  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • Recombinant Fusion Proteins