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Cancer Chemother Pharmacol. 2016 Sep;78(3):577-84. doi: 10.1007/s00280-016-3108-5. Epub 2016 Jul 23.

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

Author information

1
Division of Hematology/Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA. Muhammad.Beg@UTSouthwestern.edu.
2
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 N. Broadway, Baltimore, MD, 21231, USA.
3
Division of Hematology/Oncology, University of California San Diego Health System, 3855 Health Sciences Drive, La Jolla, CA, 92093, USA.
4
Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA.
5
Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA.
6
Division of Hematology/Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 384, Durham, NC, 27710, USA.

Abstract

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.

KEYWORDS:

Clinical trial; Colon cancer; Immunotherapy; Monoclonal antibody; Pancreatic cancer

PMID:
27449137
PMCID:
PMC5238716
DOI:
10.1007/s00280-016-3108-5
[Indexed for MEDLINE]
Free PMC Article

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