A phase I/II multicenter study of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic (PC) and colorectal cancer (CC)

240 Background: NPC-1C (NEO102) is a novel chimeric monoclonal antibody that recognizes a variant form of MUC5AC expressed specifically by human pancreatic (P) and colorectal (CC) tumors. The mechanism of action is through Antibody-dependent cell-mediated cytotoxicity (ADCC). We are presenting results of dose escalation and preplanned expansion cohort of NEO-102. Methods: This is a Phase Ib/IIa, open label, multicenter clinical trial and expansion cohort of NEO102. Patients are preselected based on an Immunuhistochemistry (IHC) companion diagnostic assay. Antigen expression cut off was set at 20% expression. NEO102 was administered every 2 weeks IV with tumor assessments every 8 weeks. The primary objective was to determine safety and tolerability of NEO102. Secondary objectives include overall survival, clinical benefit, pharmacokinetics and explore the immunologic correlates. Results: Twenty-six patients (3 pancreatic and 23 colon cancer) are evaluable for toxicity and response. Median age is 55 (32 - 68) years, 14 are male. Two dose limiting toxicities were experienced at 4.0 mg/kg: grade 3 hyperbilirubinemia (n=4) and grade 3 anemia (n=1). The maximum tolerated dose (MTD) and recommended phase-2 dose (RP2D) was established at 3.0 mg/kg. Of 12 patients evaluated for response, 5 demonstrated stable disease by RECIST (42%; 4 CC, 1 P) after the first course (Day 57) and 1 PC had SD after the second course (Day 114). OS is 4.5+ months (1+ - 13.5+), median duration of treatment of 74+ days (36-133). Of those screened, 60-70% tumors were IHC positive. Immune correlates (including cytokine profile, HAMA) will be presented. Conclusions: Treatment with NEO102 is well tolerated with a manageable safety profile. RP2D is 3.0 mg/kg. Preliminary results with NEO102 have demonstrated signs of clinical activity based on stabilization of disease in heavily pretreated patients with PC and CC. A Phase II study of NEO102 monotherapy in pancreatic and colon cancer is now enrolling patients. In addition, a combination study using NEO102 with cytotoxic chemotherapy in metastatic pancreatic cancer is underway. Clinical trial information: NCT01040000.