Abstract LB-161: A phase I safety study of NPC-1C, a novel, therapeutic antibody to treat pancreas and colorectal cancers.
Authors: Patel Sandip P. , Morse Michael A. , Diaz Luiz A. , Azad Nilofer S. , Haley Sherri , Arlen Phil M. 
Published: August 2014

Abstract
Background: NPC-1C (NEO-101; Ensituximab) is a chimeric monoclonal antibody being developed as a novel biological treatment for pancreatic and colorectal cancers. This antibody was selected from a panel of hybridomas generated from mice immunized with semi-purified membrane-associated proteins derived from biologically screened, pooled human allogeneic colon cancer tissues. The NPC-1C target appears to be a variant of MUC5AC that is expressed specifically by human pancreatic and colorectal tumors with minimal cross-reactivity to normal gastrointestinal mucosa.
Methods: A Phase 1 open label, multi-center, dose escalation clinical trial with NPC-1C treated 15 patients with advanced pancreatic and colorectal cancer who were refractory to standard therapy. The primary objectives of the Phase 1 clinical trial were 1) safety and tolerability of escalating doses of NPC-1C and 2) to assess pharmacokinetics (PK) of the antibody at each dose level. Full PK analysis of the first treatment cycle was performed. In addition, peak and trough concentrations of all subsequent cycles were evaluated. Secondary objectives evaluated for evidence of clinical benefit and to explore the immunologic correlates associated with administration of NPC-1C. Analyses of patient peripheral blood mononuclear cells (PBMCs) for antibody-dependent cell-mediated cytotoxicity (ADCC) and immune cytokine profiling utilizing the Milliplex MAP Human Cytokine/Chemokine Panel are ongoing.
Results: Three cohorts of patients were treated with NPC-1C at escalating dose levels of 1, 1.5, and 2 mg/kg IV every two weeks. All fifteen patients (10 colorectal, 5 pancreatic) have completed the study (4/15 non-evaluable). Two patients at the 1mg/kg and one patient at the 2mg/kg demonstrated stable disease at the initial restaging scans. At the 2 mg/kg dose level, at escalating rates of infusion, 3 patients experienced mild to moderate hemolysis that resolved without intervention. Six patients received 1.5 mg/kg at a constant rate of infusion have been evaluated, with no dose limiting toxicity (DLT). One patient re-staged in the 1.5 mg/kg cohort showed stable disease. Undetectable or insignificant levels of human anti-mouse antibody (HAMA) in serum were observed in 13 patients tested. A NPC-1C specific ELISA to assess PK has been developed and qualified. Analysis of patient serum samples for ADCC and immune cytokine profiling is currently underway.
Conclusions: NPC-1C is well tolerated at the current dose level of 1.5 mg/kg every 2 weeks with no DLT experienced in any of the 6 evaluable patients. Despite advanced disease in this patient population, preliminary signs of activity based on stabilization of disease, have been observed.
Citation Format: Sandip P. Patel, Michael A. Morse, Luiz A. Diaz, Nilofer S. Azad, Sherri Haley, Phil M. Arlen. A phase I safety study of NPC-1C, a novel, therapeutic antibody to treat pancreas and colorectal cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-161. doi:10.1158/1538-7445.AM2013-LB-161