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

Linda Garland, Barbara Gitlitz, Scot Ebbinghaus, Henry Pan, Hans De Haan, Raj K. Puri, Daniel Von Hoff, Robert Figlin

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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 × 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/m 2. 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 High NAB titers resulted in four patients being withdrawn from the study.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.

Original languageEnglish (US)
Pages (from-to)376-381
Number of pages6
JournalJournal of Immunotherapy
Issue number4
StatePublished - 2005


  • Immunotoxin
  • Non-small cell lung carcinoma
  • Phase 1
  • Renal carcinoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research


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