Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor

J Immunother. Jul-Aug 2005;28(4):376-81. doi: 10.1097/


NBI-3001 is a novel immunotoxin of attenuated Pseudomonas exotoxin fused to circularly permutated IL-4, which has shown some antitumor effects in glioblastoma multiforme with intratumoral administration. The authors evaluated the safety and tolerability of NBI-3001 administered intravenously in a dose-escalation design to patients with renal cell and non-small cell lung carcinoma whose tumors showed at least 10% IL-4 receptor expression. Cohorts of three to six patients were treated at dose levels of 0.008, 0.016, and 0.027 mg/m2 daily x 5 days every 28 days. Neutralizing antibody (NAB) titers, plasma levels of NBI-3001, and patient tolerability were monitored sequentially. 14 patients received a total of 36 cycles of NBI-3001 (range 1-6). No dose-limiting toxicities were noted at dose levels 0.008 and 0.016 mg/m2. At 0.027 mg/m2, two patients developed self-limiting, grade 3 or 4 transaminase elevation during cycle 1. NAB titers of more than 1:100 were detected in five of the seven patients treated with at least two cycles; the median titer after cycle 1 and the median maximum titer in subsequent cycles were 1:50 and approximately 1:1,710, respectively. No objective tumor responses were noted. Eight of 12 evaluable patients with renal cell carcinoma had stable disease; four patients had disease progression. High NAB titers resulted in four patients being withdrawn from the study. The dose-limiting toxicity for intravenous NBI-3001 was transaminase elevation at 0.027 mg/m2. NBI-3001 at 0.016 mg/m2 was well tolerated. Low circulating levels of NBI-3001, coupled with rising NAB titers, may have contributed to the lack of response in tumors that express IL-4R.

Publication types

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

MeSH terms

  • Aged
  • Antibody Formation / immunology
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / immunology
  • Bacterial Toxins / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Exotoxins / administration & dosage
  • Exotoxins / immunology
  • Exotoxins / therapeutic use*
  • Female
  • Humans
  • Infusions, Intravenous
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / immunology
  • Interleukin-4 / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Receptors, Interleukin-4 / analysis*
  • Treatment Outcome


  • Antineoplastic Agents
  • Bacterial Toxins
  • Exotoxins
  • Receptors, Interleukin-4
  • interleukin-4-Pseudomonas exotoxin
  • Interleukin-4