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

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.

• Authors: Muhammad S Beg, Nilofer S Azad, Sandip P Patel, Jose Torrealba, Sharon Mavroukakis, Melony A Beatson, Xue Ping Wang, Philip M Arlen, Michael A Morse
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 78 Issue 3 Pg. 577-84 (Sep 2016) ISSN: 1432-0843 [Electronic] Germany
• PMID: 27449137 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Carrier Proteins
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• NPC1 protein, human
• Niemann-Pick C1 Protein
• ensituximab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Carrier Proteins (genetics)
• Colonic Neoplasms (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Female
• Humans
• Intracellular Signaling Peptides and Proteins
• Male
• Maximum Tolerated Dose
• Membrane Glycoproteins (genetics)
• Middle Aged
• Niemann-Pick C1 Protein
• Pancreatic Neoplasms (drug therapy, pathology)
• Treatment Outcome