A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer.

Journal Article (Journal Article)

PURPOSE: NEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity. METHODS: This is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg. RESULTS: A total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer. CONCLUSIONS: Treatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies.

Full Text

Duke Authors

Cited Authors

  • Beg, MS; Azad, NS; Patel, SP; Torrealba, J; Mavroukakis, S; Beatson, MA; Wang, XP; Arlen, PM; Morse, MA

Published Date

  • September 2016

Published In

Volume / Issue

  • 78 / 3

Start / End Page

  • 577 - 584

PubMed ID

  • 27449137

Pubmed Central ID

  • PMC5238716

Electronic International Standard Serial Number (EISSN)

  • 1432-0843

Digital Object Identifier (DOI)

  • 10.1007/s00280-016-3108-5


  • eng

Conference Location

  • Germany