A phase I study of NPC-1C, a novel therapeutic antibody to treat pancreas and colorectal cancers.

Abstract

TPS141 Background: NPC-1C (N: ensituximab) is a chimeric monoclonal antibody being developed as a novel agent 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. N recognizes a unique immunogenic epitope with homology to a region of MUC5AC. This epitope is expressed by colon and pancreatic tumor tissues and cell lines. N does not cross-react with normal tissues (or MUC5AC from other types of cancers), except for occasional, weak binding to certain GI tract tissues. The N antibody shows ADCC activity against human colon and pancreatic tumor cells, but not control tumor cell lines. Human pancreatic tumor xenograft models showed significant, and reproducible, anti-tumor action, including some complete tumor regressions. Several examples of human tumor tissues stained with N showed a strong correlation of N staining against pancreatic and colon tumors (45% of tumors strongly positive). Methods: A Phase I open label, multi-center dose escalation clinical trial with N is currently accruing patients with advanced, refractory pancreatic and colorectal cancer. A standard 3+3 design with an expansion cohort of 10 pancreatic cancer patients is planned. Patients will be treated with N starting at 1 mg/kg IV q2wks; cohort 1 has been completed without DLT and cohort 2 is being accrued; patients are hospitalized for 48 hours for observation after the first dose of N. Eligibility criteria included good end organ function and performance status, >20% of tumor tissue staining positive for MUC5AC, and an exclusion for QTc prolongation or history of hemolytic episodes. The primary objectives of the trial are to determine the safety/tolerability of escalating doses of N therapy and to assess pharmacokinetics and immune responses to the antibody at each dose level. Secondary objectives are to evaluate evidence of clinical benefit, as measured by RECIST criteria, and to explore the immunologic correlates associated with administration of N therapy. Results from this trial will determine the dosage levels to be used in further trials. NCT01040000.